Bacterial Antibiotic Resistance

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 20700

Special Issue Editor


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Guest Editor
Department of Human Pathology, University of Messina, 98125 Messina, Italy
Interests: pathogenesis and diagnostics of viral; bacterial, and fungal infections; innate immunity; antibiotic resistance; COVID-19; cytokines; group streptococcal infections and the study of virulence factors involved in this disease

Special Issue Information

Dear Colleagues,

Antibiotics have made it possible to treat bacterial infections. Currently, at least 700,000 people worldwide die each year due to antimicrobial resistance (AMR). Without new and better treatments, the World Health Organization (WHO) predicts that this number could rise to 10 million by 2050, highlighting a health concern that is not of secondary importance.

In this Special Issue, we welcome the sharing of new insights into bacterial antibiotic resistance and control. We look forward to contributions in the form of Reviews, original research, and communications in the following areas:

  • Mechanisms of bacterial antibiotic resistance.
  • How bacteria acquire resistance.
  • The main difficult-to-treat antibiotic-resistant pathogens.

Dr. Giuseppe Mancuso
Guest Editor

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Published Papers (12 papers)

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Research

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13 pages, 1722 KiB  
Article
Ironing out Persisters? Revisiting the Iron Chelation Strategy to Target Planktonic Bacterial Persisters Harboured in Carbapenem-Resistant Escherichia coli
by Jia Hao Yeo, Nasren Begam, Wan Ting Leow, Jia Xuan Goh, Yang Zhong, Yiying Cai and Andrea Lay-Hoon Kwa
Microorganisms 2024, 12(5), 972; https://doi.org/10.3390/microorganisms12050972 - 12 May 2024
Viewed by 435
Abstract
Antibiotic resistance is a global health crisis. Notably, carbapenem-resistant Enterobacterales (CRE) pose a significant clinical challenge due to the limited effective treatment options. This problem is exacerbated by persisters that develop upon antibiotic exposure. Bacteria persisters can tolerate high antibiotic doses and can [...] Read more.
Antibiotic resistance is a global health crisis. Notably, carbapenem-resistant Enterobacterales (CRE) pose a significant clinical challenge due to the limited effective treatment options. This problem is exacerbated by persisters that develop upon antibiotic exposure. Bacteria persisters can tolerate high antibiotic doses and can cause recalcitrant infections, potentially developing further antibiotic resistance. Iron is a critical micronutrient for survival. We aimed to evaluate the utility of iron chelators, alone and in combination with antibiotics, in managing persisters. We hypothesized that iron chelators eradicate CRE persisters in vitro, when administered in combination with antibiotics. Our screening revealed three clinical isolates with bacteria persisters that resuscitated upon antibiotic removal. These isolates were treated with both meropenem and an iron chelator (deferoxamine mesylate, deferiprone or dexrazoxane) over 24 h. Against our hypothesis, bacteria persisters survived and resuscitated upon withdrawing both the antibiotic and iron chelator. Pursuing our aim, we next hypothesized that iron chelation is feasible as a post-antibiotic treatment in managing and suppressing persisters’ resuscitation. We exposed bacteria persisters to an iron chelator without antibiotics. Flow cytometric assessments revealed that iron chelators are inconsistent in suppressing persister resuscitation. Collectively, these results suggest that the iron chelation strategy may not be useful as an antibiotic adjunct to target planktonic bacteria persisters. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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13 pages, 4038 KiB  
Article
Characterization and Implications of IncP-2A Plasmid pMAS152 Harboring Multidrug Resistance Genes in Extensively Drug-Resistant Pseudomonas aeruginosa
by Li Mei, Yang Song, Xiao Liu, Kun Li, Xu Guo, Li Liu, Yang Liu, Zisis Kozlakidis, Io Hong Cheong, Duochun Wang and Qiang Wei
Microorganisms 2024, 12(3), 562; https://doi.org/10.3390/microorganisms12030562 - 12 Mar 2024
Viewed by 1131
Abstract
Bacterial antimicrobial resistance (AMR) poses a significant global public health challenge. The escalation of AMR is primarily attributed to the horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs), often facilitated by plasmids. This underscores the critical need for a comprehensive understanding of [...] Read more.
Bacterial antimicrobial resistance (AMR) poses a significant global public health challenge. The escalation of AMR is primarily attributed to the horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs), often facilitated by plasmids. This underscores the critical need for a comprehensive understanding of the resistance mechanisms and transmission dynamics of these plasmids. In this study, we utilized in vitro drug sensitivity testing, conjugation transfer assays, and whole-genome sequencing to investigate the resistance mechanism of an extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolate, MAS152. We specifically focused on analyzing the drug-resistant plasmid pMAS152 it harbors and its potential for widespread dissemination. Bioinformatics analysis revealed that MAS152 carries a distinct IncpP-2A plasmid, pMAS152, characterized by a 44.8 kb multidrug resistance (MDR) region. This region houses a 16S rRNA methyltransferase (16S-RMTase) gene, rmtB, conferring high-level resistance to aminoglycoside antibiotics. Notably, this region also contains an extended-spectrum β-Lactamase (ESBL) gene, blaPER-1, and an efflux pump operon, tmexCD-oprJ, which mediate resistance to β-Lactams and quinolone antibiotics, respectively. Such a combination of ARGs, unprecedented in reported plasmids, could significantly undermine the effectiveness of first-line antibiotics in treating P. aeruginosa infections. Investigation into the genetic environment of the MDR region suggests that Tn2 and IS91 elements may be instrumental in the horizontal transfer of rmtB. Additionally, a complex Class I integron with an ISCR1 structure, along with TnAs1, seems to facilitate the horizontal transfer of blaPER-1. The conjugation transfer assay, coupled with the annotation of conjugation-related genes and phylogenetic analysis, indicates that the plasmid pMAS152 functions as a conjugative plasmid, with other genus Pseudomonas species as potential hosts. Our findings provide vital insights into the resistance mechanisms and transmission potential of the XDR P. aeruginosa isolate MAS152, underlining the urgent need for novel strategies to combat the spread of AMR. This study highlights the complex interplay of genetic elements contributing to antibiotic resistance and underscores the importance of continuous surveillance of emerging ARGs in clinical isolates. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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17 pages, 4194 KiB  
Article
Characterization of Aeromonas Isolates from Ornamental Fish: Species, Virulence Genes, and Antimicrobial Susceptibility
by Carolina H. de Oliveira, Luisa Z. Moreno, Pedro H. M. Cardoso, Ana Paula S. Silva, Vasco T. M. Gomes, Mikaela R. F. Barbosa, Simone C. Balian and Andrea M. Moreno
Microorganisms 2024, 12(1), 176; https://doi.org/10.3390/microorganisms12010176 - 16 Jan 2024
Viewed by 945
Abstract
This study aimed to characterize 300 Aeromonas spp. strains isolated from 123 ornamental fish of 32 different species presenting with septicemia, skin lesions, and/or eye lesions. Within the 300 strains, 53.0% were identified as A. veronii, 41.3% as A. hydrophila, and [...] Read more.
This study aimed to characterize 300 Aeromonas spp. strains isolated from 123 ornamental fish of 32 different species presenting with septicemia, skin lesions, and/or eye lesions. Within the 300 strains, 53.0% were identified as A. veronii, 41.3% as A. hydrophila, and 5.7% as A. caviae. Among the six virulence genes investigated, the most frequent were act (90.3%) and aer (79.3%). More than 50% of A. hydrophila strains were positive for all the studied genes. A total of 30 virulence profiles were identified, with the five main profiles identified comprising 75% of strains. Only five strains were negative for all genes and were identified as A. caviae and A. veronii. The antimicrobial susceptibility profile was performed for 234 strains, with sulfonamides presenting more than 50% of the resistance rates. Susceptibility was observed mainly for cephalosporins, aminoglycosides, chloramphenicol and piperacillin-tazobactam. Multidrug resistance was detected in 82.5% of the studied strains, including A. caviae with 100% multidrug resistance, and A. hydrophila with 90.9% multidrug resistance. The SE-AFLP analysis resulted in 66 genotypes of A. hydrophila, 118 genotypes of A. veronii, and 14 genotypes of A. caviae, demonstrating the greater heterogeneity of A. veronii and A. caviae. However, no direct correlation was observed between the genotypes and the strains’ origins or virulence and resistance profiles. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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17 pages, 3805 KiB  
Article
Antibacterial, Resistance Modulation, Anti-Biofilm Formation, and Efflux Pump Inhibition Properties of Loeseneriella africana (Willd.) N. Halle (Celastraceae) Stem Extract and Its Constituents
by Daniel Anokwah, Evelyn Asante-Kwatia, Jonathan Asante, Daniel Obeng-Mensah, Cynthia Amaning Danquah, Isaac Kingsley Amponsah, Elvis Ofori Ameyaw, Robert Peter Biney, Ernest Obese, Lukas Oberer, Daniel Gyamfi Amoako, Akebe Luther King Abia and Abraham Yeboah Mensah
Microorganisms 2024, 12(1), 7; https://doi.org/10.3390/microorganisms12010007 - 19 Dec 2023
Viewed by 966
Abstract
This study investigated the antibacterial, resistance modulation, biofilm inhibition, and efflux pump inhibition potentials of Loeseneriella africana stem extract and its constituents. The antimicrobial activity was investigated by the high-throughput spot culture growth inhibition (HT-SPOTi) and broth microdilution assays. The resistance modulation activity [...] Read more.
This study investigated the antibacterial, resistance modulation, biofilm inhibition, and efflux pump inhibition potentials of Loeseneriella africana stem extract and its constituents. The antimicrobial activity was investigated by the high-throughput spot culture growth inhibition (HT-SPOTi) and broth microdilution assays. The resistance modulation activity was investigated using the anti-biofilm formation and efflux pump inhibition assays. Purification of the extract was carried out by chromatographic methods, and the isolated compounds were characterized based on nuclear magnetic resonance, Fourier transform infrared and mass spectrometry spectral data and comparison with published literature. The whole extract, methanol, ethyl acetate, and pet-ether fractions of L. africana all showed antibacterial activity against the test bacteria with MICs ranging from 62.5 to 500.0 µg/mL The whole extract demonstrated resistance modulation effect through strong biofilm inhibition and efflux pump inhibition activities against S. aureus ATCC 25923, E. coli ATCC 25922 and P. aeruginosa ATCC 27853. Chromatographic fractionation of the ethyl acetate fraction resulted in the isolation of a triterpenoid (4S,4αS,6αR,6βS,8αS,12αS,12βR,14αS,14βR)-4,4α,6β,8α,11,11,12β,14α-Octamethyloctadecahydropicene-1,3(2H,4H)-dione) and a phytosterol (β-sitosterol). These compounds showed antibacterial activity against susceptible bacteria at a MIC range of 31–125 µg/mL and potentiated the antibacterial activity of amoxicillin (at ¼ MIC of compounds) against E. coli and P. aeruginosa with modulation factors of 32 and 10, respectively. These compounds also demonstrated good anti-biofilm formation effect at a concentration range of 3–100 µg/mL, and bacterial efflux pump inhibition activity at ½ MIC and ¼ MIC against E. coli and P. aeruginosa. Loeseneriella africana stem bark extracts and constituents elicit considerable antibacterial, resistance modulation, and biofilm and efflux pump inhibition activities. The results justify the indigenous uses of L. africana for managing microbial infections. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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15 pages, 1447 KiB  
Article
Characteristics, Whole-Genome Sequencing and Pathogenicity Analysis of Escherichia coli from a White Feather Broiler Farm
by Shaopeng Wu, Lulu Cui, Yu Han, Fang Lin, Jiaqi Huang, Mengze Song, Zouran Lan and Shuhong Sun
Microorganisms 2023, 11(12), 2939; https://doi.org/10.3390/microorganisms11122939 - 7 Dec 2023
Viewed by 978
Abstract
Avian colibacillosis, caused by avian Escherichia coli (E. coli), has historically been one of the most prevalent infectious diseases in large-scale poultry production, causing growth delays and mortality in chickens, resulting in huge economic losses. In recent years, the widespread use [...] Read more.
Avian colibacillosis, caused by avian Escherichia coli (E. coli), has historically been one of the most prevalent infectious diseases in large-scale poultry production, causing growth delays and mortality in chickens, resulting in huge economic losses. In recent years, the widespread use of antibiotics has led to the emergence of multidrug resistance in E. coli as a significant global problem and long-term challenge. Resistant E. coli can be transmitted to humans through animal products or the environment, which presents significant public health concerns and food safety issues. In this study, we analyzed the features of 135 E. coli strains obtained from a white feather broiler farm in Shandong, China, including antimicrobial susceptibility tests, detection of class 1 integrons, drug resistance genes, virulence genes, and phylogenetic subgroups. It is particularly worrying that all 135 E. coli strains were resistant to at least five antibiotic agents, and 100% of them were multidrug-resistant (MDR). Notably, the resistance genes of blaTEM, blaCTX-M, qnrS, aaC4, tetA, and tetB exhibited a high prevalence of carriage among the tested resistance genes. However, mcr-2~mcr-9 were not detected, while the prevalence of mcr-1 was found to be 2.96%. The most common virulence genes detected were EAST1 (14.07%, encoding enterotoxins) and fyuA (14.81%, encoding biofilm formation). Phylogenetic subgroup analysis revealed that E. coli belonging to groups B2 and D, which are commonly associated with high virulence, constituted 2.22% and 11.11%, respectively. The positive rate of class 1 integrons was 31.1%. Whole-genome sequencing (WGS) and animal experiments were performed on a unique isolated strain called 21EC78 with an extremely strong membrane-forming capacity. The WGS results showed that 21EC78 carried 11 drug resistance genes and 16 virulence genes. Animal experiments showed that intraperitoneal injection with 2 × 105 CFU could cause the death of one-day-old SPF chickens in 3 days. However, the mortality of Luhua chickens was comparatively lower than that of SPF chickens. This study reports the isolation of multidrug-resistant E. coli strains in poultry, which may pose a potential threat to human health via the food chain. Furthermore, the findings of this study enhance our comprehension of the frequency and characteristics of multidrug-resistant E. coli in poultry farms, emphasizing the urgent need for improved and effective continuous surveillance to control its dissemination. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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19 pages, 24456 KiB  
Article
Transcriptome Analysis Reveals the Involvement of Mitophagy and Peroxisome in the Resistance to QoIs in Corynespora cassiicola
by Bingxue Sun, Rongjia Zhou, Guangxue Zhu, Xuewen Xie, Ali Chai, Lei Li, Tengfei Fan, Baoju Li and Yanxia Shi
Microorganisms 2023, 11(12), 2849; https://doi.org/10.3390/microorganisms11122849 - 23 Nov 2023
Viewed by 805
Abstract
Quinone outside inhibitor fungicides (QoIs) are crucial fungicides for controlling plant diseases, but resistance, mainly caused by G143A, has been widely reported with the high and widespread use of QoIs. However, two phenotypes of Corynespora casiicola (RI and RII) with the same G143A [...] Read more.
Quinone outside inhibitor fungicides (QoIs) are crucial fungicides for controlling plant diseases, but resistance, mainly caused by G143A, has been widely reported with the high and widespread use of QoIs. However, two phenotypes of Corynespora casiicola (RI and RII) with the same G143A showed significantly different resistance to QoIs in our previous study, which did not match the reported mechanisms. Therefore, transcriptome analysis of RI and RII strains after trifloxystrobin treatment was used to explore the new resistance mechanism in this study. The results show that 332 differentially expressed genes (DEGs) were significantly up-regulated and 448 DEGs were significantly down-regulated. The results of GO and KEGG enrichment showed that DEGs were most enriched in ribosomes, while also having enrichment in peroxide, endocytosis, the lysosome, autophagy, and mitophagy. In particular, mitophagy and peroxisome have been reported in medicine as the main mechanisms of reactive oxygen species (ROS) scavenging, while the lysosome and endocytosis are an important organelle and physiological process, respectively, that assist mitophagy. The oxidative stress experiments showed that the oxidative stress resistance of the RII strains was significantly higher than that of the RI strains: specifically, it was more than 1.8-fold higher at a concentration of 0.12% H2O2. This indicates that there is indeed a significant difference in the scavenging capacity of ROS between the two phenotypic strains. Therefore, we suggest that QoIs’ action caused a high production of ROS, and that scavenging mechanisms such as mitophagy and peroxisomes functioned in RII strains to prevent oxidative stress, whereas RI strains were less capable of resisting oxidative stress, resulting in different resistance to QoIs. In this study, it was first revealed that mitophagy and peroxisome mechanisms available for ROS scavenging are involved in the resistance of pathogens to fungicides. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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15 pages, 6822 KiB  
Article
Genetic- and Fiber-Diet-Mediated Changes in Antibiotic Resistance Genes in Pig Colon Contents and Feces and Their Driving Factors
by Tao Wang, Yuheng Luo, Xiangfeng Kong, Bing Yu, Ping Zheng, Zhiqing Huang, Xiangbing Mao, Jie Yu, Junqiu Luo, Hui Yan and Jun He
Microorganisms 2023, 11(10), 2370; https://doi.org/10.3390/microorganisms11102370 - 22 Sep 2023
Cited by 2 | Viewed by 827
Abstract
Comprehensive studies on the effects of genetics and fiber diets on antibiotic resistance genes (ARGs) remain scarce. In this study, we analyzed the profiles of ARGs in colonic contents and fecal samples of Taoyuan, Duroc, and Xiangcun pigs (n = 10) fed at [...] Read more.
Comprehensive studies on the effects of genetics and fiber diets on antibiotic resistance genes (ARGs) remain scarce. In this study, we analyzed the profiles of ARGs in colonic contents and fecal samples of Taoyuan, Duroc, and Xiangcun pigs (n = 10) fed at different fiber levels. Through macrogenomic analysis, we identified a total of 850 unique types of ARGs and classified them into 111 drug resistance classes. The abundance of partially drug-resistant ARGs was higher in the colonic contents of local pig breeds under a large-scale farming model. ARGs were found to be widely distributed among a variety of bacteria, predominantly in the phyla Firmicutes, Proteobacteria, and Bacteroidetes. Fiber diets reduce the abundance of ARGs in colonic contents and feces, and mobile genetic elements (MGEs) and short-chain fatty acids (SCFAs) are important drivers in mediating the effect of fiber diets on the abundance of ARGs. In vitro fermentation experiments confirmed that butyric acid significantly reduced the abundance of ARGs. In summary, the results of this study enhanced our understanding of the distribution and composition of ARGs in the colon of different breeds of pigs and revealed that a fiber diet can reduce ARGs in feces through its Butyric acid, providing reference data for environmental safety. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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21 pages, 4518 KiB  
Article
Isolation and Characterization of the Acadevirus Members BigMira and MidiMira Infecting a Highly Pathogenic Proteus mirabilis Strain
by Jéssica Duarte da Silva, Lene Bens, Adriele J. do Carmo Santos, Rob Lavigne, José Soares, Luís D. R. Melo, Marta Vallino, Roberto Sousa Dias, Zuzanna Drulis-Kawa, Sérgio Oliveira de Paula and Jeroen Wagemans
Microorganisms 2023, 11(9), 2141; https://doi.org/10.3390/microorganisms11092141 - 23 Aug 2023
Viewed by 1616
Abstract
Proteus mirabilis is an opportunistic pathogen and is responsible for more than 40% of all cases of catheter-associated urinary tract infections (CAUTIs). Healthcare-associated infections have been aggravated by the constant emergence of antibiotic-resistant bacterial strains. Because of this, the use of phages to [...] Read more.
Proteus mirabilis is an opportunistic pathogen and is responsible for more than 40% of all cases of catheter-associated urinary tract infections (CAUTIs). Healthcare-associated infections have been aggravated by the constant emergence of antibiotic-resistant bacterial strains. Because of this, the use of phages to combat bacterial infections gained renewed interest. In this study, we describe the biological and genomic features of two P. mirabilis phages, named BigMira and MidiMira. These phages belong to the Acadevirus genus (family Autographiviridae). BigMira and MidiMira are highly similar, differing only in four missense mutations in their phage tail fiber. These mutations are sufficient to impact the phages’ depolymerase activity. Subsequently, the comparative genomic analysis of ten clinical P. mirabilis strains revealed differences in their antibiotic resistance profiles and lipopolysaccharide locus, with the latter potentially explaining the host range data of the phages. The massive presence of antimicrobial resistance genes, especially in the phages’ isolation strain P. mirabilis MCS, highlights the challenges in treating infections caused by multidrug-resistant bacteria. The findings reinforce BigMira and MidiMira phages as candidates for phage therapy purposes. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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Review

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20 pages, 1842 KiB  
Review
Application of CRISPR-Cas System to Mitigate Superbug Infections
by Ali A. Rabaan, Mona A. Al Fares, Manar Almaghaslah, Tariq Alpakistany, Nawal A. Al Kaabi, Saleh A. Alshamrani, Ahmad A. Alshehri, Ibrahim Abdullah Almazni, Ahmed Saif, Abdulrahim R. Hakami, Faryal Khamis, Mubarak Alfaresi, Zainab Alsalem, Zainab A. Alsoliabi, Kawthar Amur Salim Al Amri, Amal K. Hassoueh, Ranjan K. Mohapatra, Kovy Arteaga-Livias and Mohammed Alissa
Microorganisms 2023, 11(10), 2404; https://doi.org/10.3390/microorganisms11102404 - 26 Sep 2023
Viewed by 2152
Abstract
Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type [...] Read more.
Multidrug resistance in bacterial strains known as superbugs is estimated to cause fatal infections worldwide. Migration and urbanization have resulted in overcrowding and inadequate sanitation, contributing to a high risk of superbug infections within and between different communities. The CRISPR-Cas system, mainly type II, has been projected as a robust tool to precisely edit drug-resistant bacterial genomes to combat antibiotic-resistant bacterial strains effectively. To entirely opt for its potential, advanced development in the CRISPR-Cas system is needed to reduce toxicity and promote efficacy in gene-editing applications. This might involve base-editing techniques used to produce point mutations. These methods employ designed Cas9 variations, such as the adenine base editor (ABE) and the cytidine base editor (CBE), to directly edit single base pairs without causing DSBs. The CBE and ABE could change a target base pair into a different one (for example, G-C to A-T or C-G to A-T). In this review, we addressed the limitations of the CRISPR/Cas system and explored strategies for circumventing these limitations by applying diverse base-editing techniques. Furthermore, we also discussed recent research showcasing the ability of base editors to eliminate drug-resistant microbes. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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16 pages, 961 KiB  
Review
The Challenge of Overcoming Antibiotic Resistance in Carbapenem-Resistant Gram-Negative Bacteria: “Attack on Titan”
by Giuseppe Mancuso, Silvia De Gaetano, Angelina Midiri, Sebastiana Zummo and Carmelo Biondo
Microorganisms 2023, 11(8), 1912; https://doi.org/10.3390/microorganisms11081912 - 27 Jul 2023
Cited by 6 | Viewed by 3450
Abstract
The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multidrug-resistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to [...] Read more.
The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multidrug-resistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance genes, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these “titans” of antibiotic resistance. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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17 pages, 2628 KiB  
Review
Outer Membrane Porins Contribute to Antimicrobial Resistance in Gram-Negative Bacteria
by Gang Zhou, Qian Wang, Yingsi Wang, Xia Wen, Hong Peng, Ruqun Peng, Qingshan Shi, Xiaobao Xie and Liangqiu Li
Microorganisms 2023, 11(7), 1690; https://doi.org/10.3390/microorganisms11071690 - 28 Jun 2023
Cited by 11 | Viewed by 5001
Abstract
Gram-negative bacteria depend on their cell membranes for survival and environmental adaptation. They contain two membranes, one of which is the outer membrane (OM), which is home to several different outer membrane proteins (Omps). One class of important Omps is porins, which mediate [...] Read more.
Gram-negative bacteria depend on their cell membranes for survival and environmental adaptation. They contain two membranes, one of which is the outer membrane (OM), which is home to several different outer membrane proteins (Omps). One class of important Omps is porins, which mediate the inflow of nutrients and several antimicrobial drugs. The microorganism’s sensitivity to antibiotics, which are predominantly targeted at internal sites, is greatly influenced by the permeability characteristics of porins. In this review, the properties and interactions of five common porins, OmpA, OmpC, OmpF, OmpW, and OmpX, in connection to porin-mediated permeability are outlined. Meanwhile, this review also highlighted the discovered regulatory characteristics and identified molecular mechanisms in antibiotic penetration through porins. Taken together, uncovering porins’ functional properties will pave the way to investigate effective agents or approaches that use porins as targets to get rid of resistant gram-negative bacteria. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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Other

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11 pages, 769 KiB  
Brief Report
In Vitro Susceptibility to Ceftazidime-Avibactam and Comparator Antimicrobial Agents of Carbapenem-Resistant Enterobacterales Isolates
by Tze-Peng Lim, Jun-Yuan Ho, Jocelyn Qi-Min Teo, James Heng-Chiak Sim, Si-Hui Tan, Thuan-Tong Tan and Andrea Lay-Hoon Kwa
Microorganisms 2023, 11(9), 2158; https://doi.org/10.3390/microorganisms11092158 - 25 Aug 2023
Cited by 1 | Viewed by 1359
Abstract
The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA [...] Read more.
The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA and comparator antimicrobial agents against 858 CRE isolates, arising from the Southeast Asian region, collected from a large tertiary hospital in Singapore. These CRE isolates mainly comprised Klebsiella pneumoniae (50.5%), Escherichia coli (29.4%), and Enterobacter cloacae complex (17.1%). Susceptibility rates to levofloxacin, imipenem, meropenem, doripenem, aztreonam, piperacillin/tazobactam, cefepime, tigecycline, and polymyxin B were low. CZA was the most active β-lactam agent against 68.9% of the studied isolates, while amikacin was the most active agent among all comparator antibiotics (80% susceptibility). More than half of the studied isolates (51.4%) identified were Klebsiella pneumoniae carbapenemase (KPC)-2 producers, 25.9% were New Delhi metallo-β-lactamase (NDM) producers, and Oxacillinase (OXA)-48-like producers made up 10.7%. CZA was the most active β-lactam agent against KPC-2, OXA-48-like, and Imipenemase (IMI) producers (99.3% susceptible; MIC50/90: ≤1/2 mg/L). CZA had excellent activity against the non-carbapenemase-producing CRE (91.4% susceptible; MIC50/90: ≤1/8 mg/L). Expectedly, CZA had no activity against the metallo-β-lactamases (MBL)-producing CRE (NDM- and Imipenemase MBL (IMP) producers; 27.2% isolates), and the carbapenemase co-producing CRE (NDM + KPC, NDM + OXA-48-like, NDM + IMP; 3.0% isolates). CZA is a promising addition to our limited armamentarium against CRE infections, given the reasonably high susceptibility rates against these CRE isolates. Careful stewardship and rational dosing regimens are required to preserve CZA’s utility against CRE infections. Full article
(This article belongs to the Special Issue Bacterial Antibiotic Resistance)
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