Antibiotics

23 pages, 910 KiB

Open AccessReview

Do Iron Oxide Nanoparticles Have Significant Antibacterial Properties?

by Sergey V. Gudkov, Dmitriy E. Burmistrov, Dmitriy A. Serov, Maksim B. Rebezov, Anastasia A. Semenova and Andrey B. Lisitsyn

Antibiotics 2021, 10(7), 884; https://doi.org/10.3390/antibiotics10070884 - 20 Jul 2021

Cited by 118 | Viewed by 6983

Abstract

The use of metal oxide nanoparticles is one of the promising ways for overcoming antibiotic resistance in bacteria. Iron oxide nanoparticles (IONPs) have found wide applications in different fields of biomedicine. Several studies have suggested using the antimicrobial potential of IONPs. Iron is [...] Read more.

The use of metal oxide nanoparticles is one of the promising ways for overcoming antibiotic resistance in bacteria. Iron oxide nanoparticles (IONPs) have found wide applications in different fields of biomedicine. Several studies have suggested using the antimicrobial potential of IONPs. Iron is one of the key microelements and plays an important role in the function of living systems of different hierarchies. Iron abundance and its physiological functions bring into question the ability of iron compounds at the same concentrations, on the one hand, to inhibit the microbial growth and, on the other hand, to positively affect mammalian cells. At present, multiple studies have been published that show the antimicrobial effect of IONPs against Gram-negative and Gram-positive bacteria and fungi. Several studies have established that IONPs have a low toxicity to eukaryotic cells. It gives hope that IONPs can be considered potential antimicrobial agents of the new generation that combine antimicrobial action and high biocompatibility with the human body. This review is intended to inform readers about the available data on the antimicrobial properties of IONPs, a range of susceptible bacteria, mechanisms of the antibacterial action, dependence of the antibacterial action of IONPs on the method for synthesis, and the biocompatibility of IONPs with eukaryotic cells and tissues. Full article

(This article belongs to the Special Issue Antibiotic-Free Antibacterial Strategies Enabled by Nanomaterials)

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19 pages, 3709 KiB

Open AccessArticle

Nationwide Assessment of Water Quality in Rivers across Lebanon by Quantifying Fecal Indicators Densities and Profiling Antibiotic Resistance of Escherichia coli

by Lea A. Dagher, Jouman Hassan, Samer Kharroubi, Hadi Jaafar and Issmat I. Kassem

Antibiotics 2021, 10(7), 883; https://doi.org/10.3390/antibiotics10070883 - 20 Jul 2021

Cited by 28 | Viewed by 6432

Abstract

The use of contaminated water has been associated with severe disease outbreaks. Due to widespread pollution with untreated sewage, concerns have been raised over water quality in Lebanon, a country with well-documented challenges in infrastructure. Here, we evaluated the water quality of major [...] Read more.

The use of contaminated water has been associated with severe disease outbreaks. Due to widespread pollution with untreated sewage, concerns have been raised over water quality in Lebanon, a country with well-documented challenges in infrastructure. Here, we evaluated the water quality of major rivers in Lebanon by quantifying the densities of fecal indicator bacteria (fecal coliforms and Escherichia coli). Additionally, we assessed the dissemination of antibiotic-resistant E. coli in river water. Composite water samples (n = 132) were collected from fourteen rivers, and 378 E. coli were isolated and analyzed. Fecal coliforms and E. coli were detected in 96.29% and 95.5% of the samples, respectively. Additionally, 73.48–61.3% and 31.81% of the samples exceeded the microbiological acceptability standards for irrigation and the fecal coliform limit for recreational activities, respectively. The E. coli exhibited resistance to ampicillin (40% of isolates), amoxicillin + clavulanic acid (42%), cefepime (4%), cefotaxime (14%), cefalexin (46%), cefixime (17%), doripenem (0.3%), imipenem (0.5%), gentamicin (6%), kanamycin (9%), streptomycin (35%), tetracycline (35%), ciprofloxacin (10%), norfloxacin (7%), trimethoprim-sulfamethoxazole (32%), and chloramphenicol (13%). Notably, 45.8% of the isolates were classified as multidrug resistant (MDR). Our results highlight the need to urgently address fecal pollution and the dissemination of antibiotic resistance in Lebanese rivers. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and the Environment: One Health Approach)

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17 pages, 831 KiB

Open AccessArticle

Occurrence of Rare Pathogens at the Site of Periprosthetic Hip and Knee Joint Infections: A Retrospective, Single-Center Study

by Konstantinos Anagnostakos, Christoph Grzega, Ismail Sahan, Udo Geipel and Sören L. Becker

Antibiotics 2021, 10(7), 882; https://doi.org/10.3390/antibiotics10070882 - 20 Jul 2021

Cited by 7 | Viewed by 4250

Abstract

The frequency and clinical relevance of rare pathogens at the site of periprosthetic infections of the hip and knee joint and their antibiotic resistance profiles have not yet been assessed in-depth. We retrospectively analyzed all periprosthetic hip and knee joint infections that occurred [...] Read more.

The frequency and clinical relevance of rare pathogens at the site of periprosthetic infections of the hip and knee joint and their antibiotic resistance profiles have not yet been assessed in-depth. We retrospectively analyzed all periprosthetic hip and knee joint infections that occurred between 2016 and 2020 in a single center in southwest Germany. Among 165 infections, 9.7% were caused by rare microorganisms such as Veilonella sp., Pasteurella sp., Pantoea sp., Citrobacter koseri, Serratia marcescens, Parvimonas micra, Clostridium difficile, Finegoldia magna, Morganella morganii, and yeasts. No resistance to piperacillin/tazobactam, carbapenemes, fluoroquinolones, or gentamicin was observed. Some bacteria displayed resistance to ampicillin, ampicillin/sulbactam, and cefuroxime. We present follow-up data of patients with infections due to rare pathogens and discuss the importance of close, interdisciplinary collaboration between orthopedic surgeons and clinical microbiologists to carefully select the most appropriate anti-infective treatment regimens for the increasing number of patients with such infections. Full article

(This article belongs to the Special Issue Antibiotics in Orthopedic Infections)

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12 pages, 1595 KiB

Open AccessArticle

High Prevalence of ESBL and Plasmid-Mediated Quinolone Resistance Genes in Salmonella enterica Isolated from Retail Meats and Slaughterhouses in Egypt

by Wesam A. Adel, Ashraf M. Ahmed, Yamen Hegazy, Helmy A. Torky and Tadashi Shimamoto

Antibiotics 2021, 10(7), 881; https://doi.org/10.3390/antibiotics10070881 - 20 Jul 2021

Cited by 11 | Viewed by 2719

Abstract

The emergence and spread of multidrug-resistant Salmonella enterica (S. enterica) to humans through food of animal origin are considered a major global public health concern. Currently, little is known about the prevalence of important antimicrobial resistance genes in S. enterica from [...] Read more.

The emergence and spread of multidrug-resistant Salmonella enterica (S. enterica) to humans through food of animal origin are considered a major global public health concern. Currently, little is known about the prevalence of important antimicrobial resistance genes in S. enterica from retail food in Africa. Therefore, the screening and characterization of the extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance (PMQR) genes in S. enterica isolated from retail meats and slaughterhouses in Egypt were done by using PCR and DNA sequencing techniques. Twenty-eight out of thirty-four (82.4%) non-duplicate S. enterica isolates showed multidrug-resistance phenotypes to at least three classes of antimicrobials, and fourteen (41.2%) exhibited an ESBL-resistance phenotype and harbored at least one ESBL-encoding gene. The identified β-lactamase-encoding genes included bla_CTX-M-1, bla_CTX-M-3, bla_CTX-M-13, bla_CTX-M-14, bla_CTX-M-15, and bla_SHV-12 (ESBL types); bla_CMY-2 (AmpC type); and bla_TEM-1 and bla_OXA-1 (narrow-spectrum types). PMQR genes (included qnrA, qnrB, qnrS, and aac(6′)-Ib-cr) were identified in 23 (67.6%) isolates. The presence of ESBL- and PMQR-producing S. enterica with a high prevalence rate in retail meats and slaughterhouses is considered a major threat to public health as these strains with resistance genes could be transmitted to humans through the food chain. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

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11 pages, 622 KiB

Open AccessArticle

In Vitro Synergy of Colistin in Combination with Meropenem or Tigecycline against Carbapenem-Resistant Acinetobacter baumannii

by Jacinda C. Abdul-Mutakabbir, Juwon Yim, Logan Nguyen, Philip T. Maassen, Kyle Stamper, Zain Shiekh, Razieh Kebriaei, Ryan K. Shields, Mariana Castanheira, Keith S. Kaye and Michael J. Rybak

Antibiotics 2021, 10(7), 880; https://doi.org/10.3390/antibiotics10070880 - 20 Jul 2021

Cited by 15 | Viewed by 2978

Abstract

Acinetobacter baumannii is currently classified as one of six pathogens that contribute to increased patient mortality. Thus, exploratory studies navigating alternative treatment strategies are of supreme interest. Herein, we completed minimum inhibitory concentration (MIC) testing, and time-kill analyses (TKA) on 50 carbapenem-resistant Acinetobacter [...] Read more.

Acinetobacter baumannii is currently classified as one of six pathogens that contribute to increased patient mortality. Thus, exploratory studies navigating alternative treatment strategies are of supreme interest. Herein, we completed minimum inhibitory concentration (MIC) testing, and time-kill analyses (TKA) on 50 carbapenem-resistant Acinetobacterbaumannii isolates including 28 colistin-resistant isolates. Upon testing of MEM or TGC in the presence of sub-inhibitory COL against the 50 isolates, there was a median 2-fold reduction in MEM and TGC MICs. In the TKAs, the COL+MEM combination was synergistic in 45 (90%) isolates and bactericidal in 43 (86%) isolates at 24 hours, whereas the COL+TGC combination TKAs demonstrated synergy in 32 (64%) isolates and bactericidal activity was shown in 28 (56%) isolates. Additionally, sulbactam (SUL) and TGC were added to the COL+MEM dual therapy regimen to assess the possible utility of a triple therapy regimen against five non-responsive isolates. The COL+MEM+SUL and COL+MEM+TGC regimens effectively restored synergy in (5/5) 100% of the isolates. The results of this study demonstrate the potential utility of COL combinations in the treatment of carbapenem-resistant isolates. Full article

(This article belongs to the Special Issue Combination Therapy of Antimicrobial)

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13 pages, 1728 KiB

Open AccessArticle

Staphylococcal Biofilm on the Surface of Catheters: Electron Microscopy Evaluation of the Inhibition of Biofilm Growth by RNAIII Inhibiting Peptide

by Adilson de Oliveira, Luiza Pinheiro-Hubinger, Valéria Cataneli Pereira, Danilo Flávio Moraes Riboli, Katheryne Benini Martins, Letícia Calixto Romero and Maria de Lourdes Ribeiro de Souza da Cunha

Antibiotics 2021, 10(7), 879; https://doi.org/10.3390/antibiotics10070879 - 20 Jul 2021

Cited by 2 | Viewed by 2620

Abstract

Staphylococcus aureus and coagulase-negative staphylococci (CoNS) have become the main causative agents of medical device-related infections due to their biofilm-forming capability, which protects them from the host’s immune system and from the action of antimicrobials. This study evaluated the ability of RNA III [...] Read more.

Staphylococcus aureus and coagulase-negative staphylococci (CoNS) have become the main causative agents of medical device-related infections due to their biofilm-forming capability, which protects them from the host’s immune system and from the action of antimicrobials. This study evaluated the ability of RNA III inhibiting peptide (RIP) to inhibit biofilm formation in 10 strains isolated from clinical materials, including one S. aureus strain, two S. epidermidis, two S. haemolyticus, two S. lugdunensis, and one isolate each of the following species: S. warneri, S. hominis, and S. saprophyticus. The isolates were selected from a total of 200 strains evaluated regarding phenotypic biofilm production and the presence and expression of the ica operon. The isolates were cultured in trypticase soy broth with 2% glucose in 96-well polystyrene plates containing catheter segments in the presence and absence of RIP. The catheter segments were observed by scanning electron microscopy. The results showed inhibition of biofilm formation in the presence of RIP in all CoNS isolates; however, RIP did not interfere with biofilm formation by S. aureus. RIP is a promising tool that might be used in the future for the prevention of biofilm-related infections caused by CoNS. Full article

(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)

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11 pages, 269 KiB

Open AccessArticle

Perspectives of Healthcare Professionals Regarding Factors Associated with Antimicrobial Resistance (AMR) and Their Consequences: A Cross Sectional Study in Eastern Province of Saudi Arabia

by Mohamed A. Baraka, Amany Alboghdadly, Samar Alshawwa, Asim Ahmed Elnour, Hassan Alsultan, Taha Alsalman, Hussain Alaithan, Md. Ashraful Islam, Kareem Ahmed El-Fass, Yehia Mohamed, Abdulsalam A. Alasseri and Khairi Mustafa Fahelelbum

Antibiotics 2021, 10(7), 878; https://doi.org/10.3390/antibiotics10070878 - 19 Jul 2021

Cited by 8 | Viewed by 3377

Abstract

Factors reported in the literature associated with inappropriate prescribing of antimicrobials include physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians’ decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. [...] Read more.

Factors reported in the literature associated with inappropriate prescribing of antimicrobials include physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians’ decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing antimicrobials would minimize the risk of resistance and, consequently, improve patients’ clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. A cross-sectional study was conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed, validated, and piloted survey specific with closed-ended questions. A value of p < 0.05 was considered to be statistically significant. All data analysis was performed using the Statistical Package for Social Sciences (IBM SPSS version 23.0). 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All of the respondents acknowledged effectiveness, previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) as being key factors influencing physicians’ choice during antimicrobial prescribing. The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials were reported to be common practices. Furthermore, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials, and the use of antimicrobials without a physician’s prescription (i.e., self-medication) represent key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines. Full article

(This article belongs to the Special Issue Current and Novel Antimicrobial Strategies for Bacterial and Fungal Infections by Resistant Organisms)

16 pages, 11140 KiB

Open AccessArticle

Pseudomonas aeruginosa PAO 1 In Vitro Time–Kill Kinetics Using Single Phages and Phage Formulations—Modulating Death, Adaptation, and Resistance

by Ana Mafalda Pinto, Alberta Faustino, Lorenzo M. Pastrana, Manuel Bañobre-López and Sanna Sillankorva

Antibiotics 2021, 10(7), 877; https://doi.org/10.3390/antibiotics10070877 - 19 Jul 2021

Cited by 7 | Viewed by 3406

Abstract

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted [...] Read more.

Pseudomonas aeruginosa is responsible for nosocomial and chronic infections in healthcare settings. The major challenge in treating P. aeruginosa-related diseases is its remarkable capacity for antibiotic resistance development. Bacteriophage (phage) therapy is regarded as a possible alternative that has, for years, attracted attention for fighting multidrug-resistant infections. In this work, we characterized five phages showing different lytic spectrums towards clinical isolates. Two of these phages were isolated from the Russian Microgen Sextaphage formulation and belong to the Phikmvviruses, while three Pbunaviruses were isolated from sewage. Different phage formulations for the treatment of P. aeruginosa PAO1 resulted in diversified time–kill outcomes. The best result was obtained with a formulation with all phages, prompting a lower frequency of resistant variants and considerable alterations in cell motility, resulting in a loss of 73.7% in swimming motility and a 79% change in swarming motility. These alterations diminished the virulence of the phage-resisting phenotypes but promoted their growth since most became insensitive to a single or even all phages. However, not all combinations drove to enhanced cell killings due to the competition and loss of receptors. This study highlights that more caution is needed when developing cocktail formulations to maximize phage therapy efficacy. Selecting phages for formulations should consider the emergence of phage-resistant bacteria and whether the formulations are intended for short-term or extended antibacterial application. Full article

(This article belongs to the Special Issue Phage Therapy to Control Pathogenic Bacteria)

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14 pages, 2293 KiB

Open AccessArticle

Blood Cultures and Appropriate Antimicrobial Administration after Achieving Sustained Return of Spontaneous Circulation in Adults with Nontraumatic Out-of-Hospital Cardiac Arrest

by Chih-Hao Lin, Po-Lin Chen, Yi-Tzu Huang, Ching-Yu Ho, Chih-Chia Hsieh, William Yu Chung Wang, Ching-Chi Lee and Wen-Chien Ko

Antibiotics 2021, 10(7), 876; https://doi.org/10.3390/antibiotics10070876 - 19 Jul 2021

Cited by 2 | Viewed by 1878

Abstract

We aimed to determine the incidence of bacteremia and prognostic effects of prompt administration of appropriate antimicrobial therapy (AAT) on nontraumatic out-of-hospital cardiac arrest (OHCA) patients achieving a sustained return of spontaneous circulation (sROSC), compared with non-OHCA patients. In the multicenter case-control study, [...] Read more.

We aimed to determine the incidence of bacteremia and prognostic effects of prompt administration of appropriate antimicrobial therapy (AAT) on nontraumatic out-of-hospital cardiac arrest (OHCA) patients achieving a sustained return of spontaneous circulation (sROSC), compared with non-OHCA patients. In the multicenter case-control study, nontraumatic OHCA adults with bacteremia episodes after achieving sROSC were defined as case patients, and non-OHCA patients with community-onset bacteremia in the emergency department were regarded as control patients. Initially, case patients had a higher bacteremia incidence than non-OHCA visits (231/2171, 10.6% vs. 10,430/314,620, 3.3%; p < 0.001). Compared with the matched control (2288) patients, case (231) patients experienced more bacteremic episodes due to low respiratory tract infections, fewer urosepsis events, fewer Escherichia coli bacteremia, and more streptococcal and anaerobes bacteremia. Antimicrobial-resistant organisms, such as methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacteriaceae, were frequently evident in case patients. Notably, each hour delay in AAT administration was associated with an average increase of 10.6% in crude 30-day mortality rates in case patients, 0.7% in critically ill control patients, and 0.3% in less critically ill control patients. Conclusively, the incidence and characteristics of bacteremia differed between the nontraumatic OHCA and non-OHCA patients. The incorporation of blood culture samplings and rapid AAT administration as first-aids is essential for nontraumatic OHCA patients after achieving sROSC. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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10 pages, 758 KiB

Open AccessArticle

An Application of Imipenem Discs or P. aeruginosa ATCC 27853 Reference Strain Increases Sensitivity of Carbapenem Inactivation Method for Non-Fermenting Gram-Negative Bacteria

by Tomasz Bogiel, Mateusz Rzepka and Eugenia Gospodarek-Komkowska

Antibiotics 2021, 10(7), 875; https://doi.org/10.3390/antibiotics10070875 - 19 Jul 2021

Cited by 2 | Viewed by 2574

Abstract

Non-fermenting Gram-negative rods are one of the most commonly isolated bacteria from human infections. These microorganisms are typically opportunistic pathogens that pose a serious threat to public health due to possibility of transmission in the human population. Resistance to beta-lactams, due to carbapenemases [...] Read more.

Non-fermenting Gram-negative rods are one of the most commonly isolated bacteria from human infections. These microorganisms are typically opportunistic pathogens that pose a serious threat to public health due to possibility of transmission in the human population. Resistance to beta-lactams, due to carbapenemases synthesis, is one of the most important antimicrobial resistance mechanisms amongst them. The aim of this study was to evaluate the usefulness of the Carbapenem Inactivation Method (CIM), and its modifications, for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. This research involved 81 strains of Gram-negative rods. Of the tested strains, 55 (67.9%) synthesized carbapenemases. For non-fermenting rods, 100% sensitivity and specificity was obtained in the version of the CIM test using imipenem discs and E. coli ATCC 25922 strain. The CIM test allows for differentiation of carbapenems resistance mechanisms resulting from carbapenemase synthesis from other resistance types. It is a reliable diagnostic method for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. Application of imipenem discs and P. aeruginosa ATCC 27853 reference strain increases CIM results sensitivity, while imipenem discs and E. coli ATCC 25922 strain use maintains full precision of the test for non-fermenting rods. Full article

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18 pages, 1689 KiB

Open AccessArticle

Subinhibitory Antibiotic Concentrations Enhance Biofilm Formation of Clinical Enterococcus faecalis Isolates

by Sara Bernardi, Annette Anderson, Guido Macchiarelli, Elmar Hellwig, Fabian Cieplik, Kirstin Vach and Ali Al-Ahmad

Antibiotics 2021, 10(7), 874; https://doi.org/10.3390/antibiotics10070874 - 19 Jul 2021

Cited by 34 | Viewed by 3983

Abstract

Enterococcus faecalis is a microorganism that can be found in the oral cavity, especially in secondary endodontic infections, with a prevalence ranging from 24–70%. The increase in the ability to form biofilms in the presence of subinhibitory antibiotic concentrations is a phenomenon that [...] Read more.

Enterococcus faecalis is a microorganism that can be found in the oral cavity, especially in secondary endodontic infections, with a prevalence ranging from 24–70%. The increase in the ability to form biofilms in the presence of subinhibitory antibiotic concentrations is a phenomenon that is observed for a wide variety of bacterial pathogens and is associated with increased resistance. In this study, therefore, six E. faecalis isolates from an endodontic environment and two control strains were exposed to subinhibitory concentrations of Penicillin G, Amoxicillin, Doxycycline, Fosfomycin, Tetracycline and Vancomycin and examined for their biofilm formation abilities. The minimum inhibitory concentration (MIC) was determined for all E. faecalis isolates. A culture of the isolate was mixed with a serial dilution series of the respective antibiotic, incubated overnight and the biofilm formation was analyzed using a microtiter plate assay. All isolates were able to form biofilms in the absence of an antibiotic. A significant increase in biofilm formation of up to more than 50% was found in the isolates exposed to subinhibitory concentrations of various antibiotics. Most isolates showed a significant increase in Fosfomycin (7/8), Doxycycline (6/8) and Tetracycline (6/8). Three endodontic isolates showed a significant increase in five of the antibiotics examined at the same time. On exposure to Vancomycin, three endodontic isolates and the two control strains showed an increase. The increase in the ability to form biofilms extended over a concentration range from 1/2 to 1/64 of the MIC concentration. Antibiotics may reach certain niches in the oral cavity at subinhibitory concentrations only. This can increase the biofilm formation by enterococci, and in turn lead to decreased susceptibility of these taxa to antibiotics. Full article

(This article belongs to the Special Issue Oral Microorganisms and Inactivation of Oral Biofilms)

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8 pages, 677 KiB

Open AccessEditor’s ChoicePerspective

Biosynthetic Potential of Streptomyces Rationalizes Genome-Based Bioprospecting

by Balasubramanian Cibichakravarthy and Polapass Arul Jose

Antibiotics 2021, 10(7), 873; https://doi.org/10.3390/antibiotics10070873 - 19 Jul 2021

Cited by 4 | Viewed by 2735

Abstract

Streptomyces are the most prolific source of structurally diverse microbial natural products. Advancing genome-based analysis reveals the previously unseen potential of Streptomyces to produce numerous novel secondary metabolites, which allows us to take natural product discovery to the next phase. However, at present [...] Read more.

Streptomyces are the most prolific source of structurally diverse microbial natural products. Advancing genome-based analysis reveals the previously unseen potential of Streptomyces to produce numerous novel secondary metabolites, which allows us to take natural product discovery to the next phase. However, at present there is a huge disproportion between the rate of genome reports and discovery of new compounds. From this perspective of harnessing the enduring importance of Streptomyces, we discuss the recent genome-directed advancements inspired by hidden biosynthetic wealth that provide hope for future antibiotics. Full article

(This article belongs to the Special Issue Discovery and Biosynthesis of Novel Antibiotic from Streptomyces)

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12 pages, 2776 KiB

Open AccessArticle

MCR Expression Conferring Varied Fitness Costs on Host Bacteria and Affecting Bacteria Virulence

by Wan Li, Zhihai Liu, Wenjuan Yin, Lu Yang, Lu Qiao, Shikai Song, Zhuoren Ling, Ruicheng Zheng, Congming Wu, Yang Wang and Jianzhong Shen

Antibiotics 2021, 10(7), 872; https://doi.org/10.3390/antibiotics10070872 - 19 Jul 2021

Cited by 12 | Viewed by 2758

Abstract

Since the first report of the plasmid-mediated, colistin-resistant gene, mcr-1, nine mcr genes and their subvariants have been identified. The spreading scope of mcr-1~10 varies greatly, suggesting that mcr-1~10 may have different evolutionary advantages. Depending on MCR family phylogeny, mcr-6 is highly [...] Read more.

Since the first report of the plasmid-mediated, colistin-resistant gene, mcr-1, nine mcr genes and their subvariants have been identified. The spreading scope of mcr-1~10 varies greatly, suggesting that mcr-1~10 may have different evolutionary advantages. Depending on MCR family phylogeny, mcr-6 is highly similar to mcr-1 and -2, and mcr-7~10 are highly similar to mcr-3 and -4. We compared the expression effects of MCR-1~5 on bacteria of common physiological background. The MCR-1-expressing strain showed better growth than did MCR-2~5-expressing strains in the presence of colistin. LIVE/DEAD staining analysis revealed that MCR-3~5 expression exerted more severe fitness burdens on bacteria than did MCR-1 and -2. Bacteria expressing MCRs except MCR-2 showed enhanced virulence with increased epithelial penetration ability determined by trans-well model (p < 0.05). Enhanced virulence was also observed in the Galleria mellonella model, which may have resulted from bacterial membrane damage and different levels of lipopolysaccharide (LPS) release due to MCR expression. Collectively, MCR-1-expressing strain showed the best survival advantage of MCR-1~5-expressing strains, which may partly explain the worldwide distribution of mcr-1. Our results suggested that MCR expression may cause increased bacterial virulence, which is alarming, and further attention will be needed to focus on the control of infectious diseases caused by mcr-carrying pathogens. Full article

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15 pages, 1666 KiB

Open AccessArticle

Tackling Virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon

by Mohammed F. Aldawsari, El-Sayed Khafagy, Ahmed Al Saqr, Ahmed Alalaiwe, Hisham A. Abbas, Moataz A. Shaldam, Wael A. H. Hegazy and Reham M. Goda

Antibiotics 2021, 10(7), 871; https://doi.org/10.3390/antibiotics10070871 - 17 Jul 2021

Cited by 37 | Viewed by 2932

Abstract

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. [...] Read more.

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics. Full article

(This article belongs to the Special Issue Plants, Algae and Fungi Extracts: Promising Resources in the Fight against Pathogens)

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14 pages, 1598 KiB

Open AccessArticle

Antibacterial Peptides Produced by Alcalase from Cowpea Seed Proteins

by Ali Osman, Gamal Enan, Abdul-Raouf Al-Mohammadi, Seham Abdel-Shafi, Samar Abdel-Hameid, Mahmoud Z. Sitohy and Nashwa El-Gazzar

Antibiotics 2021, 10(7), 870; https://doi.org/10.3390/antibiotics10070870 - 17 Jul 2021

Cited by 22 | Viewed by 2786

Abstract

Cowpea seed protein hydrolysates (CPH) were output from cowpea seeds applying alcalase^® from Bacillus licheniformis. CPH with an elevated level of hydrolysis was fractionated by size exclusion chromatography (SEC). Both CPH and SEC-portions showed to contain antimicrobial peptides (AMPs) as they [...] Read more.

Cowpea seed protein hydrolysates (CPH) were output from cowpea seeds applying alcalase^® from Bacillus licheniformis. CPH with an elevated level of hydrolysis was fractionated by size exclusion chromatography (SEC). Both CPH and SEC-portions showed to contain antimicrobial peptides (AMPs) as they inhibited both Gram-positive bacteria, such as Listeria monocytogenes LMG10470 (L. monocytogenes), Listeria innocua. LMG11387 (L. innocua), Staphylococcus aureus ATCC25923 (S.aureus), and Streptococcus pyogenes ATCC19615 (St.pyogenes), and Gram-negative bacteria, such as Klebsiella pnemoniae ATCC43816 (K. pnemoniae), Pseudomonas aeroginosa ATCC26853 (P. aeroginosa), Escherichia coli ATCC25468) (E.coli) and Salmonella typhimurium ATCC14028 (S. typhimurium).The data exhibited that both CPH and size exclusion chromatography-fraction 1 (SEC-F1) showed high antibacterial efficiency versus almost all the assessed bacteria. The MIC of the AMPs within SEC-F1 and CPHs were (25 µg/mL) against P. aeruginosa, E.coli and St. pyogenes. However, higher MICsof approximately 100–150 µg/mL showed for both CPHs and SEC-F1 against both S. aureus and L. innocua; it was 50 µg/mL of CPH against S.aureus. The Electro-spray-ionization-mass-spectrometry (ESI-MS) of fraction (1) revealed 10 dipeptides with a molecular masses arranged from 184 Da to 364 Da and one Penta peptide with a molecular mass of approximately 659 Da inthe case of positive ions. While the negative ions showed 4 dipeptides with the molecular masses that arranged from 330 Da to 373 Da. Transmission electron microscope (TEM) demonstrated that the SEC-F1 induced changes in the bacterial cells affected. Thus, the results suggested that the hydrolysis of cowpea seed proteins by Alcalase is an uncomplicated appliance to intensify its antibacterial efficiency. Full article

(This article belongs to the Special Issue Mechanisms of Antimicrobial Peptides on Pathogens)

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17 pages, 4016 KiB

Open AccessArticle

Efficiency of Antimicrobial Photodynamic Therapy with Photodithazine^® on MSSA and MRSA Strains

by Beatriz Müller Nunes Souza, Juliana Guerra Pinto, André Henrique Correia Pereira, Alejandro Guillermo Miñán and Juliana Ferreira-Strixino

Antibiotics 2021, 10(7), 869; https://doi.org/10.3390/antibiotics10070869 - 17 Jul 2021

Cited by 9 | Viewed by 2861

Abstract

Staphylococccus aureus is a ubiquitous and opportunistic bacteria associated with high mortality rates. Antimicrobial photodynamic therapy (aPDT) is based on the application of a light source and a photosensitizer that can interact with molecular oxygen, forming Reactive Oxygen Species (ROS) that result in [...] Read more.

Staphylococccus aureus is a ubiquitous and opportunistic bacteria associated with high mortality rates. Antimicrobial photodynamic therapy (aPDT) is based on the application of a light source and a photosensitizer that can interact with molecular oxygen, forming Reactive Oxygen Species (ROS) that result in bacterial inactivation. This study aimed to analyze, in vitro, the action of aPDT with Photodithazine^® (PDZ) in methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains. The strains were incubated with PDZ at 25, 50, 75, and 100 mg/L for 15 min and irradiated with fluences of 25, 50, and 100 J/cm². The internalization of PDZ was evaluated by confocal microscopy, the bacterial growth by counting the number of colony-forming units, as well as the bacterial metabolic activity post-aPDT and the production of ROS. In both strains, the photosensitizer was internalized; the production of ROS increased when the aPDT was applied; there was a bacterial reduction compared to the control at all the evaluated fluences and concentrations; and, in most parameters, it was obtained complete inactivation with significant difference (p < 0.05). The implementation of aPDT with PDZ in clinical strains of S. aureus has resulted in its complete inactivation, including the MRSA strains. Full article

(This article belongs to the Special Issue New and Innovative Applications of Antimicrobial Photodynamic Therapy)

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19 pages, 2994 KiB

Open AccessArticle

Prevalence and Antimicrobial Resistance of Klebsiella Strains Isolated from a County Hospital in Romania

by Alice Elena Ghenea, Ramona Cioboată, Andrei Ioan Drocaş, Eugen Nicolae Țieranu, Corina Maria Vasile, Aritina Moroşanu, Cristian George Țieranu, Alex-Ioan Salan, Mihaela Popescu, Adriana Turculeanu, Vlad Padureanu, Anca-Loredana Udriștoiu, Daniela Calina, Dan Cȃrţu and Ovidiu Mircea Zlatian

Antibiotics 2021, 10(7), 868; https://doi.org/10.3390/antibiotics10070868 - 16 Jul 2021

Cited by 18 | Viewed by 3375

Abstract

The study evaluated the evolution of the incidence of infections with Klebsiella in the County Clinical Emergency Hospital of Craiova (SCJUC), Romania. Also, we monitored antibiotic resistance over more than two years and detected changes in resistance to various antimicrobial agents. Our study [...] Read more.

The study evaluated the evolution of the incidence of infections with Klebsiella in the County Clinical Emergency Hospital of Craiova (SCJUC), Romania. Also, we monitored antibiotic resistance over more than two years and detected changes in resistance to various antimicrobial agents. Our study included 2062 patients (823 women and 1239 men) hospitalised in SCJUC during the period 1st of September 2017 to 30 June 2019. In 458 patients (22.21%) from the 2062 total patients, the collected samples (1116) were positive and from those, we isolated 251 strains of Klebsiella spp. We conducted a longitudinal analysis of the prevalence of Klebsiella spp. over calendar months, which showed a prevalence in surgical wards that ranged between 5.25% and 19.49% in June 2018, while in medical wards the variation was much wider, between 5.15% and 17.36% in April 2018. Klebsiella spp. strains showed significant resistance to Amoxicillin/Clavulanate, Aztreonam and Cephalosporins such as Ceftriaxone, Ceftazidime and Cefepime. We examined the possible link with the consumption of antibiotics in the same month by performing a multiple linear regression analysis. The evolution of antibiotic resistance in Klebsiella was correlated with the variation of resistance in other bacteria, which suggests common resistance mechanisms in the hospital environment. By performing the regression for dependency between antibiotic resistance and antibiotic consumption, we observed some correlations between antibiotic consumption and the development of antibiotic resistance after 1, 2 and even 3 months (e.g., resistance to meropenem was influenced by the consumption in the hospital ward of imipenem 1 month and two months before, but only 1 month before by the consumption of meropenem). The clustering of strains showed filiation between multiresistant Klebsiella spp. strains isolated from specific patients from the ICU. The evolution of prevalence and antibiotic resistance in Klebsiella correlated with the resistance in other bacteria, which suggest common resistance mechanisms in the hospital environment, and also with the consumption of antibiotics. Full article

(This article belongs to the Special Issue Healthcare Infections, Healthcare Environment and Antimicrobial Resistance)

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11 pages, 469 KiB

Open AccessArticle

Evaluating the Implementation of a Pilot Quality Improvement Program to Support Appropriate Antimicrobial Prescribing in General Practice

by Ruby Biezen, Kirsty Buising, Tim Monaghan, Rachael Ball, Karin Thursky, Ron Cheah, Malcolm Clark and Jo-Anne Manski-Nankervis

Antibiotics 2021, 10(7), 867; https://doi.org/10.3390/antibiotics10070867 - 16 Jul 2021

Cited by 6 | Viewed by 3436

Abstract

Inappropriate antimicrobial prescribing contributes to increasing antimicrobial resistance. An antimicrobial stewardship (AMS) program in the form of quality improvement activities that included audit and feedback, clinical decision support and education was developed to help optimise prescribing in general practice. The aim of this [...] Read more.

Inappropriate antimicrobial prescribing contributes to increasing antimicrobial resistance. An antimicrobial stewardship (AMS) program in the form of quality improvement activities that included audit and feedback, clinical decision support and education was developed to help optimise prescribing in general practice. The aim of this study was to evaluate the implementation of this program (Guidance GP) in three general practices in Melbourne, Australia, between November 2019 and August 2020. Thirty-one general practitioners (GPs) participated in the program, with 11 GPs and three practice managers participating in follow-up focus groups and interviews to explore the acceptability and feasibility of the program. Our findings showed that the quality improvement activities were acceptable to GPs, if they accurately fit GPs’ decision-making process and workflow. It was also important that they provided clinically meaningful information in the form of audit and feedback to GPs. The time needed to coordinate the program, and costs to implement the program were some of the potential barriers identified. Facilitators of success were a “whole of practice” approach with enthusiastic GPs and practice staff, and an identified practice champion. The findings of this research will inform implementation strategies for both the Guidance GP program and AMS programs more broadly in Australian general practice, which will be critical for general practice participation and engagement. Full article

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10 pages, 391 KiB

Open AccessArticle

Assessing Knowledge and Perception Regarding Antimicrobial Stewardship and Antimicrobial Resistance in University Students of Pakistan: Findings and Implications

by Iltaf Hussain, Nisa Yousaf, Sana Haider, Pervisha Jalil, Muhammad Usman Saleem, Imran Imran, Abdul Majeed, Anees ur Rehman, Muhammad Uzair, Muhammad Fawad Rasool, Faleh Alqahtani and Hussain Alqhtani

Antibiotics 2021, 10(7), 866; https://doi.org/10.3390/antibiotics10070866 - 16 Jul 2021

Cited by 4 | Viewed by 3338

Abstract

The irrational use of antimicrobials has enormously contributed to antimicrobial resistance (AMR) globally and especially in the developing world. To assess the knowledge and perception regarding AMR and antimicrobial stewardship (AMS), a descriptive cross-sectional study was carried out in university students enrolled in [...] Read more.

The irrational use of antimicrobials has enormously contributed to antimicrobial resistance (AMR) globally and especially in the developing world. To assess the knowledge and perception regarding AMR and antimicrobial stewardship (AMS), a descriptive cross-sectional study was carried out in university students enrolled in pharmacy, veterinary, and biology programs by using an online self-administered questionnaire. The Chi-square and Fisher exact tests (where applicable) were performed to assess the association of the demographics with the students’ knowledge and perception regarding AMR and AMS. A total of 496 students completed the questionnaire, among which, 85.7% of the participants were familiar with the term AMR and 79.4% of the participants correctly identified a poorly designed dosing regimen as a contributing factor towards AMR. The majority of participants (57.9%) were familiar with the term AMS and 86.5% were aware of the aim of AMS. The participants showed good knowledge regarding AMR and AMS, but to further improve student knowledge and perception of AMS and AMR, it is suggested that dedicated modules on antibiotic use and AMS should be incorporated into the curricula of these undergraduate and postgraduate programs. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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12 pages, 2052 KiB

Open AccessReview

Antimicrobial Activity of Calcium Silicate-Based Dental Materials: A Literature Review

by Ana Cristina Padilha Janini, Gabriela Fernanda Bombarda, Lauter Eston Pelepenko and Marina Angélica Marciano

Antibiotics 2021, 10(7), 865; https://doi.org/10.3390/antibiotics10070865 - 16 Jul 2021

Cited by 12 | Viewed by 2901

Abstract

Endodontic biomaterials have significantly improved dental treatment techniques in several aspects now that they can be used for vital pulp treatments, as temporary intracanal medication, in definitive fillings, in apical surgeries, and for regenerative procedures. Calcium silicate-based cement is a class of dental [...] Read more.

Endodontic biomaterials have significantly improved dental treatment techniques in several aspects now that they can be used for vital pulp treatments, as temporary intracanal medication, in definitive fillings, in apical surgeries, and for regenerative procedures. Calcium silicate-based cement is a class of dental material that is used in endodontics in direct contact with the dental structures, connective tissue, and bone. Because the material interacts with biological tissues and stimulates biomineralization processes, its properties are of major importance. The main challenge in endodontic treatments is the elimination of biofilms that are present in the root canal system anatomical complexities, as it remains even after chemical-mechanical preparation and disinfection procedures. Thus, an additional challenge for these biomaterials is to exert antimicrobial activity while maintaining their biological properties in parallel. This article reviews the literature for studies considering the antimicrobial properties of calcium silicate-based dental biomaterials used in endodontic practice. Considering the reviewed studies, it can be affirmed that the reduced antimicrobial effect exhibited by calcium silicate-based endodontic materials clearly emphasizes that all clinical procedures prior to their use must be carefully performed. Future studies for the evaluation of these materials, and especially newly proposed materials, under poly-microbial biofilms associated with endodontic diseases will be necessary. Full article

(This article belongs to the Special Issue Development of Antimicrobial Biomaterials and Natural Alternatives against Biofilms and Implant-Related Infections)

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8 pages, 943 KiB

Open AccessArticle

Antibiotic Prescriptions for Respiratory Tract Viral Infections in the Colombian Population

by Manuel E. Machado-Duque, Diego Arturo García, Melissa Hiromi Emura-Velez, Andrés Gaviria-Mendoza, Claudia Giraldo-Giraldo and Jorge E. Machado-Alba

Antibiotics 2021, 10(7), 864; https://doi.org/10.3390/antibiotics10070864 - 16 Jul 2021

Cited by 2 | Viewed by 2271

Abstract

Antimicrobials are frequently inappropriately prescribed for the management of upper respiratory tract infections (URTIs); therefore, the frequency of antibiotic prescriptions for patients with viral URTIs was assessed in this study. A cross-sectional study, including ambulatory patients diagnosed with viral URTI, was conducted, and [...] Read more.

Antimicrobials are frequently inappropriately prescribed for the management of upper respiratory tract infections (URTIs); therefore, the frequency of antibiotic prescriptions for patients with viral URTIs was assessed in this study. A cross-sectional study, including ambulatory patients diagnosed with viral URTI, was conducted, and records of antimicrobial prescriptions were obtained. Sociodemographic, clinical (diagnostic), and pharmacological (antimicrobial) variables were assessed. Through multivariate analysis, variables associated with the use of antibiotics for viral infections were identified. A total of 341,182 patients with viral URTIs were identified. The patients, who were from 26 different departments of Colombia, had a mean age of 29.7 ± 23.5 years and a female predominance of 58.7% (n = 200,195). The most frequent viral infections were as follows: acute rhinopharyngitis (common cold) (n = 206,211; 60.4%); unspecified acute tonsillitis (n = 27,432; 8.0%); and acute pharyngitis (n = 26,411; 7.7%). A total of 24.8% of the patients (n = 84,453) received a prescription for antibiotics, predominantly penicillins (n = 61,871; 18.1%) and cephalosporins (n = 10,926; 3.2%). Patients treated in Atlántico, Valle, and Risaralda departments, along with those older than 5 years, were more likely to receive antibiotics for the treatment of viral infections. Antibiotics are frequently prescribed for the management of URTIs, which is considered an inappropriate practice due to a lack of clinical benefits, increased generation of antimicrobial resistance, and a risk of adverse reactions due to the use of medications that patients do not require. Drug utilization studies are a great tool for monitoring how antibiotics are being used and planning interventions to improve their use. Full article

(This article belongs to the Special Issue 10th Anniversary of Antibiotics — Recent Advances in Rational Antimicrobial Use)

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25 pages, 465 KiB

Open AccessEditor’s ChoiceReview

Role of RND Efflux Pumps in Drug Resistance of Cystic Fibrosis Pathogens

by Viola Camilla Scoffone, Gabriele Trespidi, Giulia Barbieri, Samuele Irudal, Elena Perrin and Silvia Buroni

Antibiotics 2021, 10(7), 863; https://doi.org/10.3390/antibiotics10070863 - 15 Jul 2021

Cited by 19 | Viewed by 4014

Abstract

Drug resistance represents a great concern among people with cystic fibrosis (CF), due to the recurrent and prolonged antibiotic therapy they should often undergo. Among Multi Drug Resistance (MDR) determinants, Resistance-Nodulation-cell Division (RND) efflux pumps have been reported as the main contributors, due [...] Read more.

Drug resistance represents a great concern among people with cystic fibrosis (CF), due to the recurrent and prolonged antibiotic therapy they should often undergo. Among Multi Drug Resistance (MDR) determinants, Resistance-Nodulation-cell Division (RND) efflux pumps have been reported as the main contributors, due to their ability to extrude a wide variety of molecules out of the bacterial cell. In this review, we summarize the principal RND efflux pump families described in CF pathogens, focusing on the main Gram-negative bacterial species (Pseudomonas aeruginosa, Burkholderia cenocepacia, Achromobacter xylosoxidans, Stenotrophomonas maltophilia) for which a predominant role of RND pumps has been associated to MDR phenotypes. Full article

(This article belongs to the Special Issue The Structural and Functional Study of Efflux Pumps Belonging to the RND Transporters Family from Gram-Negative Bacteria)

30 pages, 6960 KiB

Open AccessEditor’s ChoiceArticle

A Fine-Tuned Lipophilicity/Hydrophilicity Ratio Governs Antibacterial Potency and Selectivity of Bifurcated Halogen Bond-Forming NBTIs

by Anja Kolarič, Maja Kokot, Martina Hrast, Matjaž Weiss, Irena Zdovc, Jurij Trontelj, Simon Žakelj, Marko Anderluh and Nikola Minovski

Antibiotics 2021, 10(7), 862; https://doi.org/10.3390/antibiotics10070862 - 15 Jul 2021

Cited by 11 | Viewed by 5015

Abstract

Herein, we report the design of a focused library of novel bacterial topoisomerase inhibitors (NBTIs) based on innovative mainly monocyclic right-hand side fragments active against DNA gyrase and Topo IV. They exhibit a very potent and wide range of antibacterial activity, even against [...] Read more.

Herein, we report the design of a focused library of novel bacterial topoisomerase inhibitors (NBTIs) based on innovative mainly monocyclic right-hand side fragments active against DNA gyrase and Topo IV. They exhibit a very potent and wide range of antibacterial activity, even against some of the most concerning hard-to-treat pathogens for which new antibacterials are urgently needed, as reported by the WHO and CDC. NBTIs enzyme activity and whole cell potency seems to depend on the fine-tuned lipophilicity/hydrophilicity ratio that governs the permeability of those compounds through the bacterial membranes. Lipophilicity of NBTIs is apparently optimal for passing through the membrane of Gram-positive bacteria, but the higher, although not excessive lipophilicity and suitable hydrophilicity seems to determine the passage through Gram-negative bacterial membranes. However, due to the considerable hERG inhibition, which is still at least two orders of magnitude away from MICs, continued optimization is required to realize their full potential. Full article

(This article belongs to the Special Issue Design and Preparation of Antimicrobial Agents)

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20 pages, 5575 KiB

Open AccessArticle

Crosstalks between NOD1 and Histone H2A Contribute to Host Defense against Streptococcus agalactiae Infection in Zebrafish

by Xiaoman Wu, Fan Xiong, Hong Fang, Jie Zhang and Mingxian Chang

Antibiotics 2021, 10(7), 861; https://doi.org/10.3390/antibiotics10070861 - 15 Jul 2021

Cited by 3 | Viewed by 2009

Abstract

Correlation studies about NOD1 and histones have not been reported. In the present study, we report the functional correlation between NOD1 and the histone H2A variant in response to Streptococcus agalactiae infection. In zebrafish, NOD1 deficiency significantly promoted S. agalactiae proliferation and decreased [...] Read more.

Correlation studies about NOD1 and histones have not been reported. In the present study, we report the functional correlation between NOD1 and the histone H2A variant in response to Streptococcus agalactiae infection. In zebrafish, NOD1 deficiency significantly promoted S. agalactiae proliferation and decreased larval survival. Transcriptome analysis revealed that the significantly enriched pathways in NOD1^−/− adult zebrafish were mainly involved in immune and metabolism. Among 719 immunity-associated DEGs at 48 hpi, 74 DEGs regulated by NOD1 deficiency were histone variants. Weighted gene co-expression network analysis identified that H2A, H2B, and H3 had significant associations with NOD1 deficiency. Above all, S. agalactiae infection could induce the expression of intracellular histone H2A, as well as NOD1 colocalized with histone H2A, both in the cytoplasm and cell nucleus in the case of S. agalactiae infection. The overexpression of H2A variants such as zfH2A-6 protected against S. agalactiae infection and could improve cell survival in NOD1-deficient cells. Furthermore, NOD1 could interact with zfH2A-6 and cooperate with zfH2A-6 to inhibit the proliferation of S. agalactiae. NOD1 also showed a synergetic effect in inducing the expression of many antibacterial genes, especially antibacterial pattern recognition receptors PGRP2, PGRP5, and PGRP6. Collectively, these results firstly highlight the roles of NOD1 deficiency in the regulation of immune-related and metabolic pathways, and the correlation between zebrafish NOD1 and histone H2A variant in the defense against S. agalactiae infection. Full article

(This article belongs to the Special Issue Bacterial Infection and PRRs-Mediated Innate Immune Responses in Fish)

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15 pages, 1198 KiB

Open AccessArticle

Analysis of Wastewater Reveals the Spread of Diverse Extended-Spectrum β-Lactamase-Producing E. coli Strains in uMgungundlovu District, South Africa

by Siyabonga N. Gumede, Akebe L. K. Abia, Daniel G. Amoako and Sabiha Y. Essack

Antibiotics 2021, 10(7), 860; https://doi.org/10.3390/antibiotics10070860 - 15 Jul 2021

Cited by 15 | Viewed by 3075

Abstract

Wastewater treatment plants (WWTPs) are major reservoirs of antibiotic-resistant bacteria (ARB), favouring antibiotic resistance genes (ARGs) interchange among bacteria and they can provide valuable information on ARB circulating in a community. This study characterised extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli from the influent and [...] Read more.

Wastewater treatment plants (WWTPs) are major reservoirs of antibiotic-resistant bacteria (ARB), favouring antibiotic resistance genes (ARGs) interchange among bacteria and they can provide valuable information on ARB circulating in a community. This study characterised extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli from the influent and effluent of four WWTPs in uMgungundlovu District, KwaZulu-Natal, South Africa. E. coli was enumerated using the membrane filtration method and confirmed using the API 20E test and real-time polymerase chain reaction. ESBL-producers were phenotypically identified by their susceptibility to the third-generation cephalosporins using the disc diffusion and the double-disc synergy methods against cefotaxime (30 µg) with and without 10 µg clavulanic acid. Genotypic verification was by PCR of the TEM, SHV, and CTX-M genes. The clonality of isolates was assessed by ERIC-PCR. The highest E. coli count ranged between 1.1 × 10⁵ (influent) and 4.3 × 10³ CFU/mL (effluent). Eighty pure isolates were randomly selected, ten from the influent and effluent of each of the four WWTP. ESBLs were phenotypically confirmed in 49% (n = 39) of the isolates, of which 77% (n = 30) were genotypically confirmed. Seventy-three percent of the total isolates were multidrug-resistant (MDR). Only two isolates were susceptible to all antibiotics. Overall, resistance to first and second-generation cephalosporins was higher than to third and fourth generation cephalosporins. Also, 15% of the isolates were resistant to carbapenems. The CTX-M-type ESBL (67%; n = 20) was the most common ESBL antibiotic resistance gene (ARG) followed by TEM (57%; n = 17) and SHV-types (27%; n = 8). Also, a substantial number of isolates simultaneously carried all three ESBL genes. ERIC-PCR revealed a high diversity of isolates. The diversity of the isolates observed in the influent samples suggest the potential circulation of different ESBL-producing strains within the studied district, requiring a more comprehensive epidemiological study to prevent the spread of ESBL-producing bacteria within impoverished communities. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Wastewater and Its Treatment)

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18 pages, 3295 KiB

Open AccessArticle

Antibacterial Activity of Boswellia sacra Flueck. Oleoresin Extract against Porphyromonas gingivalis Periodontal Pathogen

by Nashwah G. M. Attallah, Walaa A. Negm, Engy Elekhnawy, Najla Altwaijry, Elshaymaa I. Elmongy, Thanaa A. El-Masry, Eman A. Alturki, Doaa A. Yousef and Malak Y. Shoukheba

Antibiotics 2021, 10(7), 859; https://doi.org/10.3390/antibiotics10070859 - 15 Jul 2021

Cited by 24 | Viewed by 3466

Abstract

Boswellia sacra Flueck. oleoresin extract (frankincense) has traditionally been used in the treatment of different diseases, but there are no sufficient studies on its potential activity against periodontal pathogens. Therefore, antibacterial and antibiofilm activity of frankincense extract against Porphyromonas gingivalis clinical isolates were [...] Read more.

Boswellia sacra Flueck. oleoresin extract (frankincense) has traditionally been used in the treatment of different diseases, but there are no sufficient studies on its potential activity against periodontal pathogens. Therefore, antibacterial and antibiofilm activity of frankincense extract against Porphyromonas gingivalis clinical isolates were studied. The phytochemical composition of the volatile components of the extract was identified by GC-MS analysis revealing 49 compounds as trans-nerolidyl formate, cycloartenol acetate, ursenoic acid 3-oxomethyl ester, bisabolene epoxide, and kaur-16-ene. It decreased the growth and increased the leakage of nucleotides in 58.3% and 33.3% of isolates, respectively. Additionally, it reduced the extracellular polysaccharide production and the cell surface hydrophobicity in 41.67% and 50% of the isolates, respectively. Crystal violet assay revealed inhibition of biofilm formation by the tested isolates. Light microscope and scanning electron microscope were used to examine the biofilms and they confirmed the reduction of biofilm formation by frankincense extract. Downregulation of the genes linked to biofilm formation (fimA, hagA, and hagB) was observed using qRT-PCR after treatment with the frankincense extract. This study suggested that the frankincense extract could exhibit antibacterial and antibiofilm activity against P. gingivalis isolates. Thus, the frankincense extract could be used as a treatment approach for periodontitis. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Extracts from Plant)

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13 pages, 281 KiB

Open AccessArticle

Prescribers’ Knowledge, Attitudes and Behaviors on Antibiotics, Antibiotic Use and Antibiotic Resistance in Jordan

by Reema A. Karasneh, Sayer I. Al-Azzam, Mera Ababneh, Ola Al-Azzeh, Ola B. Al-Batayneh, Suhaib M. Muflih, Mohammad Khasawneh, Abdo-Rahman M. Khassawneh, Yousef S. Khader, Barbara R. Conway and Mamoon A. Aldeyab

Antibiotics 2021, 10(7), 858; https://doi.org/10.3390/antibiotics10070858 - 15 Jul 2021

Cited by 8 | Viewed by 3952

Abstract

More research is needed on the drivers of irrational antibiotic prescribing among healthcare professionals and to ensure effective prescribing and an adequate understanding of the issue of antibiotic resistance. This study aimed at evaluating prescribers’ knowledge, attitudes and behaviors about antibiotic use and [...] Read more.

More research is needed on the drivers of irrational antibiotic prescribing among healthcare professionals and to ensure effective prescribing and an adequate understanding of the issue of antibiotic resistance. This study aimed at evaluating prescribers’ knowledge, attitudes and behaviors about antibiotic use and antibiotic resistance. A cross-sectional study was conducted utilizing an online questionnaire and included physicians and dentists from all sectors in Jordan. A total of 613 prescribers were included (physicians n = 409, dentists n = 204). Respondents’ knowledge on effective use, unnecessary use or associated side effects of antibiotics was high (>90%), compared with their knowledge on the spread of antibiotic resistance (62.2%). For ease of access to the required guidelines on managing infections, and to materials that advise on prudent antibiotic use and antibiotic resistance, prescribers agreed in 62% and 46.1% of cases, respectively. 28.4% of respondents had prescribed antibiotics when they would have preferred not to do so more than once a day or more than once a week. Among respondents who prescribed antibiotics, 63.4% would never or rarely give out resources on prudent use of antibiotics for infections. The findings are of importance to inform antibiotic stewardships about relevant interventions aimed at changing prescribers’ behaviors and improving antibiotic prescribing practices. Full article

(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship)

14 pages, 1881 KiB

Open AccessArticle

The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis

by Dillon Muzondiwa, Hleliwe Hlanze and Oleg N. Reva

Antibiotics 2021, 10(7), 857; https://doi.org/10.3390/antibiotics10070857 - 15 Jul 2021

Cited by 8 | Viewed by 2758

Abstract

Drug resistance (DR) remains a global challenge in tuberculosis (TB) control. In order to develop molecular-based diagnostic methods to replace the traditional culture-based diagnostics, there is a need for a thorough understanding of the processes that govern TB drug resistance. The use of [...] Read more.

Drug resistance (DR) remains a global challenge in tuberculosis (TB) control. In order to develop molecular-based diagnostic methods to replace the traditional culture-based diagnostics, there is a need for a thorough understanding of the processes that govern TB drug resistance. The use of whole-genome sequencing coupled with statistical and computational methods has shown great potential in unraveling the complexity of the evolution of DR-TB. In this study, we took an innovative approach that sought to determine nonrandom associations between polymorphic sites in Mycobacterium tuberculosis (Mtb) genomes. Attributable risk statistics were applied to identify the epistatic determinants of DR in different clades of Mtb and the possible evolutionary pathways of DR development. It was found that different lineages of Mtb exploited different evolutionary trajectories towards multidrug resistance and compensatory evolution to reduce the DR-associated fitness cost. Epistasis of DR acquisition is a new area of research that will aid in the better understanding of evolutionary biological processes and allow predicting upcoming multidrug-resistant pathogens before a new outbreak strikes humanity. Full article

(This article belongs to the Special Issue Antimicrobial Resistance of Mycobacterium Tuberculosis: Old and New Drugs)

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16 pages, 4179 KiB

Open AccessArticle

Elucidation of Teicoplanin Interactions with Drug Targets Related to COVID-19

by Faizul Azam

Antibiotics 2021, 10(7), 856; https://doi.org/10.3390/antibiotics10070856 - 15 Jul 2021

Cited by 23 | Viewed by 3703

Abstract

Teicoplanin is a glycopeptide antibiotic effective against several bacterial infections, has exhibited promising therapeutic efficiency against COVID-19 in vitro, and the rationale for its use in COVID-19 is yet to be recognized. Hence, in this study a number of molecular modeling techniques [...] Read more.

Teicoplanin is a glycopeptide antibiotic effective against several bacterial infections, has exhibited promising therapeutic efficiency against COVID-19 in vitro, and the rationale for its use in COVID-19 is yet to be recognized. Hence, in this study a number of molecular modeling techniques were employed to decrypt the mechanistic insight of teicoplanin interaction with several COVID-19 drug targets. Initially, molecular docking was employed to study the teicoplanin interaction with twenty-five SARS-CoV-2 structural and non-structural proteins which was followed by molecular mechanics/generalized Born surface area (MM/GBSA) computation for binding energy predictions of top ten models from each target. Amongst all macromolecular targets, the N-terminal domain of the nucleocapsid protein displayed the strongest affinity with teicoplanin showing binding energies of −7.4 and −102.13 kcal/mol, in docking and Prime MM/GBSA, respectively. Thermodynamic stability of the teicoplanin-nucleocapsid protein was further probed by molecular dynamics simulations of protein–ligand complex as well as unbounded protein in 100 ns trajectories. Post-simulation MM-GBSA computation of 50 frames extracted from simulated trajectories estimated an average binding energy of −62.52 ± 12.22 kcal/mol. In addition, conformational state of protein in complex with docked teicoplanin displayed stable root-mean-square deviation/fluctuation. In conclusion, computational investigation of the potential targets of COVID-19 and their interaction mechanism with teicoplanin can guide the design of novel therapeutic armamentarium for the treatment of SARS-CoV-2 infection. However, additional studies are warranted to establish the clinical use or relapses, if any, of teicoplanin in the therapeutic management of COVID-19 patients. Full article

(This article belongs to the Special Issue Novel Antibiotics and Novel Modes of Action to Fight Infectious Diseases in Antimicrobial Resistance Era)

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Open AccessArticle

Novel Nitro-Heteroaromatic Antimicrobial Agents for the Control and Eradication of Biofilm-Forming Bacteria

by Heidi N. Koenig, Gregory M. Durling, Danica J. Walsh, Tom Livinghouse and Philip S. Stewart

Antibiotics 2021, 10(7), 855; https://doi.org/10.3390/antibiotics10070855 - 14 Jul 2021

Cited by 4 | Viewed by 2563

Abstract

The synthesis and biological activity of several novel nitrothiazole, nitrobenzothiazole, and nitrofuran containing antimicrobial agents for the eradication of biofilm-forming Gram-negative and Gram-positive pathogens is described. Nitazoxanide (NTZ), nitrofurantoin, and furazolidone are commercial antimicrobials which were used as models to show how structural [...] Read more.

The synthesis and biological activity of several novel nitrothiazole, nitrobenzothiazole, and nitrofuran containing antimicrobial agents for the eradication of biofilm-forming Gram-negative and Gram-positive pathogens is described. Nitazoxanide (NTZ), nitrofurantoin, and furazolidone are commercial antimicrobials which were used as models to show how structural modification improved activity toward planktonic bacteria via minimum inhibitory concentration (MIC) assays and biofilms via minimum biofilm eradication concentration (MBEC) assays. Structure–activity relationship (SAR) studies illustrate the ways in which improvements have been made to the aforementioned antimicrobial agents. It is of particular interest in this regard that the introduction of a chloro substituent at the 5-position of NTZ (analog 1b) resulted in marked activity enhancement, as did the replacement of the 2-acetoxy substituent in the latter compound with a basic amine group (analog 7b). It is also of importance that analog 4a, which is a simple methacrylamide, displayed noteworthy activity against S. epidermidis biofilms. These lead compounds identified to have high activity towards biofilms provide promise as starting points in future pro-drug studies. Full article

(This article belongs to the Special Issue Antibacterial Resistance and Novel Strategies to Eradicate Bacterial Biofilms)

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Antibiotics, Volume 10, Issue 7 (July 2021) – 135 articles

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