Research

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17 pages, 2697 KiB

Open AccessArticle

Modeling Bacterial Attachment Mechanisms on Superhydrophobic and Superhydrophilic Substrates

by T. Brian Cavitt and Niyati Pathak

Pharmaceuticals 2021, 14(10), 977; https://doi.org/10.3390/ph14100977 - 26 Sep 2021

Cited by 7 | Viewed by 1777

Superhydrophilic and superhydrophobic substrates are widely known to inhibit the attachment of a variety of motile and/or nonmotile bacteria. However, the thermodynamics of attachment are complex. Surface energy measurements alone do not address the complexities of colloidal (i.e., bacterial) dispersions but do affirm [...] Read more.

Superhydrophilic and superhydrophobic substrates are widely known to inhibit the attachment of a variety of motile and/or nonmotile bacteria. However, the thermodynamics of attachment are complex. Surface energy measurements alone do not address the complexities of colloidal (i.e., bacterial) dispersions but do affirm that polar (acid-base) interactions (

Δ G^{A B}

) are often more significant than nonpolar (Lifshitz-van der Waals) interactions (

Δ G^{L W}

). Classical DLVO theory alone also fails to address all colloidal interactions present in bacterial dispersions such as

Δ G^{A B}

and Born repulsion (

Δ G^{B o r n}

) yet accounts for the significant electrostatic double layer repulsion (

Δ G^{E L}

). We purpose to model both motile (e.g., P. aeruginosa and E. coli) and nonmotile (e.g., S. aureus and S. epidermidis) bacterial attachment to both superhydrophilic and superhydrophobic substrates via surface energies and extended DLVO theory corrected for bacterial geometries. We used extended DLVO theory and surface energy analyses to characterize the following Gibbs interaction energies for the bacteria with superhydrophobic and superhydrophilic substrates:

Δ G^{L W}

,

Δ G^{A B}

,

Δ G^{E L}

, and

Δ G^{B o r n}

. The combination of the aforementioned interactions yields the total Gibbs interaction energy (

Δ G^{t o t}

) of each bacterium with each substrate. Analysis of the interaction energies with respect to the distance of approach yielded an equilibrium distance (

d_{e q}

) that seems to be independent of both bacterial species and substrate. Utilizing both

d_{e q}

and Gibbs interaction energies, substrates could be designed to inhibit bacterial attachment. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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14 pages, 2620 KiB

Open AccessArticle

Benzydamine Reverses TMexCD-TOprJ-Mediated High-Level Tigecycline Resistance in Gram-Negative Bacteria

by Ziwen Tong, Tianqi Xu, Tian Deng, Jingru Shi, Zhiqiang Wang and Yuan Liu

Pharmaceuticals 2021, 14(9), 907; https://doi.org/10.3390/ph14090907 - 07 Sep 2021

Cited by 9 | Viewed by 2568

Abstract

Recently, a novel efflux pump gene cluster called tmexCD1-toprJ1 and its variants have been identified, which undermine the antibacterial activity of tigecycline, one of the last remaining options effective against multidrug-resistant (MDR) Gram-negative bacteria. Herein, we report the potent synergistic effect of the [...] Read more.

Recently, a novel efflux pump gene cluster called tmexCD1-toprJ1 and its variants have been identified, which undermine the antibacterial activity of tigecycline, one of the last remaining options effective against multidrug-resistant (MDR) Gram-negative bacteria. Herein, we report the potent synergistic effect of the non-steroidal anti-inflammatory drug benzydamine in combination with tigecycline at sub-inhibitory concentrations against various temxCD-toprJ-positive Gram-negative pathogens. The combination of benzydamine and tigecycline killed all drug-resistant pathogens during 24 h of incubation. In addition, the evolution of tigecycline resistance was significantly suppressed in the presence of benzydamine. Studies on the mechanisms of synergism showed that benzydamine disrupted the bacterial proton motive force and the functionality of this kind of novel plasmid-encoded resistance-nodulation-division efflux pump, thereby promoting the intracellular accumulation of tigecycline. Most importantly, the combination therapy of benzydamine and tigecycline effectively improved the survival of Galleria mellonella larvae compared to tigecycline monotherapy. Our findings provide a promising drug combination therapeutic strategy for combating superbugs carrying the tmexCD-toprJ gene. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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16 pages, 3943 KiB

Open AccessArticle

Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression

by Noha E. Farag, Mohamed K. El-Kherbetawy, Hussein M. Ismail, Ahmed M. Abdelrady, Eman A. Toraih, Walid Kamal Abdelbasset, Rehab M. Lashine, Mohammed EL-dosoky, Sally Yussef Abed, Khalid M. Ibraheem, Manal S. Fawzy and Sawsan A. Zaitone

Pharmaceuticals 2021, 14(7), 597; https://doi.org/10.3390/ph14070597 - 22 Jun 2021

Cited by 5 | Viewed by 2755

Abstract

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated [...] Read more.

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with erythromycin in healthy rats. Although rats with MI did not show further elevations in fibrosis score on treatment with macrolides, they produced significant fibrosis in healthy rats. Downregulation of cardiac Nav1.5 transcript was observed following macrolides treatment in both groups (healthy rats and rats with MI). In conclusion, the current findings suggested the potential cardiotoxic effects of chronic doses of macrolide antibiotics in rats with MI as manifested by abnormal ECG changes and pathological findings in addition to downregulation of Nav1.5 channels. Furthermore, in the current dose ranges, azithromycin produced the least toxicity compared to clarithromycin and erythromycin. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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9 pages, 660 KiB

Open AccessArticle

Antibiotic Resistance Profile and Biofilm Production of Staphylococcus pseudintermedius Isolated from Dogs in Thailand

by Pavarish Jantorn, Hawaree Heemmamad, Tanawan Soimala, Saowakon Indoung, Jongkon Saising, Julalak Chokpaisarn, Warapond Wanna, Varomyalin Tipmanee and Dennapa Saeloh

Pharmaceuticals 2021, 14(6), 592; https://doi.org/10.3390/ph14060592 - 20 Jun 2021

Cited by 15 | Viewed by 3852

Abstract

Staphylococcus pseudintermedius is a zoonotic pathogen that can cause life-threatening infections in animals and humans. The study of methicillin-resistant S. pseudintermedius (MRSP) and its ability to produce biofilms is important to select the most suitable treatment. The prevalence and characteristics of S. pseudintermedius [...] Read more.

Staphylococcus pseudintermedius is a zoonotic pathogen that can cause life-threatening infections in animals and humans. The study of methicillin-resistant S. pseudintermedius (MRSP) and its ability to produce biofilms is important to select the most suitable treatment. The prevalence and characteristics of S. pseudintermedius isolated from dogs admitted at the Veterinary Teaching Hospital, Prince of Songkla University, Thailand were assessed. Results showed that 28.30% (15/53) of the isolates were MRSP. Amplification of the mecA gene was observed in 93.33% (14/15) MRSP. Methicillin-resistant strains revealed co-resistant patterns against other antibiotics, including chloramphenicol, clindamycin, tetracycline, clarithromycin, ciprofloxacin, and trimethoprim. In this study, all bacterial isolates produced biofilms, while 90.55% of S. pseudintermedius isolates were strong or moderate biofilm producers. Most (45–60%) of the resistant strains were strong biofilm producers, while the correlation between biofilm production and antibiotic resistance was not statistically significant. This is the first study in southern Thailand to investigate the drug-resistant profile of S. pseudintermedius and its ability to form biofilm. The results will contribute to a better understanding of the emergence and prevalence of antimicrobial resistance in S. pseudintermedius. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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15 pages, 729 KiB

Open AccessArticle

The Beta-Lactam Resistome Expressed by Aerobic and Anaerobic Bacteria Isolated from Human Feces of Healthy Donors

by Rosalino Vázquez-López, Sandra Solano-Gálvez, Diego Abelardo Álvarez-Hernández, Jorge Alberto Ascencio-Aragón, Eduardo Gómez-Conde, Celia Piña-Leyva, Manuel Lara-Lozano, Tayde Guerrero-González and Juan Antonio González-Barrios

Pharmaceuticals 2021, 14(6), 533; https://doi.org/10.3390/ph14060533 - 03 Jun 2021

Cited by 7 | Viewed by 3923

Abstract

Antibiotic resistance is a major health problem worldwide, causing more deaths than diabetes and cancer. The dissemination of vertical and horizontal antibiotic resistance genes has been conducted for a selection of pan-resistant bacteria. Here, we test if the aerobic and anaerobic bacteria from [...] Read more.

Antibiotic resistance is a major health problem worldwide, causing more deaths than diabetes and cancer. The dissemination of vertical and horizontal antibiotic resistance genes has been conducted for a selection of pan-resistant bacteria. Here, we test if the aerobic and anaerobic bacteria from human feces samples in health conditions are carriers of beta-lactamases genes. The samples were cultured in a brain–heart infusion medium and subcultured in blood agar in aerobic and anaerobic conditions for 24 h at 37 °C. The grown colonies were identified by their biochemical profiles. The DNA was extracted and purified by bacterial lysis using thermal shock and were used in the endpoint PCR and next generation sequencing to identify beta-lactamase genes expression (OXA, VIM, SHV, TEM, IMP, ROB, KPC, CMY, DHA, P, CFX, LAP, and BIL). The aerobic bacterias Aeromonas hydrophila, Citrobacter freundii, Proteus mirabilis, Providencia rettgeri, Serratia fonticola, Serratia liquefaciens, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Pantoea agglomerans, Enterococcus faecalis, and Enterobacter cloacae, the anaerobic bacteria: Capnocytophaga species, Bacteroides distasonis, Bifidobacterium adolescentis, Bacteroides ovatus, Bacteroides fragilis, Eubacterium species, Eubacterium aerofaciens, Peptostreptococcus anaerobius, Fusobacterium species, Bacteroides species, and Bacteroides vulgatus were isolated and identified. The results showed 49 strains resistant to beta-lactam with the expression of blaSHV (10.2%), blaTEM (100%), blaKPC (10.2%), blaCYM (14.3%), blaP (2%), blaCFX (8.2%), and blaBIL (6.1%). These data support the idea that the human enteric microbiota constitutes an important reservoir of genes for resistance to beta-lactamases and that such genes could be transferred to pathogenic bacteria. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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13 pages, 694 KiB

Open AccessArticle

In Vitro Time-Kill of Common Ocular Pathogens with Besifloxacin Alone and in Combination with Benzalkonium Chloride

by Joseph Blondeau and Heleen DeCory

Pharmaceuticals 2021, 14(6), 517; https://doi.org/10.3390/ph14060517 - 27 May 2021

Cited by 1 | Viewed by 2231

Abstract

Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of [...] Read more.

Background: Besifloxacin ophthalmic suspension 0.6% (w/v%) contains benzalkonium chloride (BAK) as a preservative. We evaluated the in vitro time-kill activity of besifloxacin, alone and in combination with BAK, against common bacteria implicated in ophthalmic infections. Methods: The activity of besifloxacin (100 µg/mL), BAK (10, 15, 20, and 100 µg/mL), and combinations of besifloxacin and BAK were evaluated against isolates of Staphylococcus epidermidis (n = 4), Staphylococcus aureus (n = 3), Haemophilus influenzae (n = 2), and Pseudomonas aeruginosa (n = 2) in time-kill experiments of 180 min duration. With the exception of one S. aureus isolate, all of the staphylococcal isolates were methicillin- and/or ciprofloxacin-resistant; one P. aeruginosa isolate was ciprofloxacin-resistant. The reductions in the viable colony counts (log₁₀ CFU/mL) were plotted against time, and the differences among the time–kill curves were evaluated using an analysis of variance. Areas-under-the-killing-curve (AUKCs) were also computed. Results: Besifloxacin alone demonstrated ≥3-log killing of P. aeruginosa (<5 min) and H. influenzae (<120 min), and approached 3-log kills of S. aureus. BAK alone demonstrated concentration-dependent killing of S. epidermidis, S. aureus and H. influenzae, and at 100 µg/mL produced ≥3-log kills in <5 min against these species. The addition of BAK (10, 15, and 20 µg/mL) to besifloxacin increased the rate of killing compared to besifloxacin alone, with earlier 3-log kills of all species except P. aeruginosa and a variable impact on S. aureus. The greatest reductions in AUKC were observed among H. influenzae (8-fold) and S. epidermidis (≥5-fold). Similar results were found when the isolates were evaluated individually by their resistance phenotype. Conclusions: In addition to confirming the activity of 100 µg/mL BAK as a preservative in the bottle, these data suggest that BAK may help besifloxacin to achieve faster time-kills on-eye in the immediate timeframe post-instillation before extensive dilution against bacterial species implicated in ophthalmic infections, including drug-resistant S. epidermidis. Greater killing activity may help prevent resistance development and/or help treat resistant organisms. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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11 pages, 1126 KiB

Open AccessArticle

Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Staphylococcus aureus Clinical Isolates

by Tanveer Ali, Abdul Basit, Asad Mustafa Karim, Jung-Hun Lee, Jeong-Ho Jeon, Shafiq ur Rehman and Sang-Hee Lee

Pharmaceuticals 2021, 14(5), 420; https://doi.org/10.3390/ph14050420 - 01 May 2021

Cited by 11 | Viewed by 4559

Abstract

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and [...] Read more.

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. Staphylococcus aureus acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the mecA gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant Staphylococcus aureus (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the mecA gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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18 pages, 2313 KiB

Open AccessArticle

Mechanism of Resistance Development in E. coli against TCAT, a Trimethoprim-Based Photoswitchable Antibiotic

by Anna I. Lauxen, Piermichele Kobauri, Michael Wegener, Mickel J. Hansen, Nicole S. Galenkamp, Giovanni Maglia, Wiktor Szymanski, Ben L. Feringa and Oscar P. Kuipers

Pharmaceuticals 2021, 14(5), 392; https://doi.org/10.3390/ph14050392 - 21 Apr 2021

Cited by 9 | Viewed by 3596

Abstract

During the last decades, a continuous rise of multi-drug resistant pathogens has threatened antibiotic efficacy. To tackle this key challenge, novel antimicrobial therapies are needed with increased specificity for the site of infection. Photopharmacology could enable such specificity by allowing for the control [...] Read more.

During the last decades, a continuous rise of multi-drug resistant pathogens has threatened antibiotic efficacy. To tackle this key challenge, novel antimicrobial therapies are needed with increased specificity for the site of infection. Photopharmacology could enable such specificity by allowing for the control of antibiotic activity with light, as exemplified by trans/cis-tetra-ortho-chloroazobenzene-trimethoprim (TCAT) conjugates. Resistance development against the on (irradiated, TCATa) and off (thermally adapted, TCATd) states of TCAT were compared to that of trimethoprim (TMP) in Escherichia coli mutant strain CS1562. Genomics and transcriptomics were used to explore the acquired resistance. Although TCAT shows TMP-like dihydrofolate reductase (DHFR) inhibition in vitro, transcriptome analyses show different responses in acquired resistance. Resistance against TCATa (on) relies on the production of exopolysaccharides and overexpression of TolC. While resistance against TCATd (off) follows a slightly different gene expression profile, both indicate hampering the entrance of the molecule into the cell. Conversely, resistance against TMP is based on alterations in cell metabolism towards a more persister-like phenotype, as well as alteration of expression levels of enzymes involved in the folate biosynthesis. This study provides a deeper understanding of the development of new therapeutic strategies and the consequences on resistance development against photopharmacological drugs. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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17 pages, 2032 KiB

Open AccessArticle

Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem–Resistant Acinetobacter baumannii

by Ozioma F. Nwabor, Pawarisa Terbtothakun, Supayang P. Voravuthikunchai and Sarunyou Chusri

Pharmaceuticals 2021, 14(3), 185; https://doi.org/10.3390/ph14030185 - 25 Feb 2021

Cited by 17 | Viewed by 2973

Abstract

The spread of multi-drug resistant (MDR) pathogens and the lagging pace in the development of novel chemotherapeutic agents warrant the use of combination therapy as a reliable, cost-effective interim option. In this study, the synergistic effects of fosfomycin in combination with other antibiotics [...] Read more.

The spread of multi-drug resistant (MDR) pathogens and the lagging pace in the development of novel chemotherapeutic agents warrant the use of combination therapy as a reliable, cost-effective interim option. In this study, the synergistic effects of fosfomycin in combination with other antibiotics were assessed. Of the 193 isolates, 90.6% were non-susceptible to fosfomycin, with minimum inhibitory concentrations (MICs) of ≥128 µg/mL. Antibacterial evaluation of fosfomycin-resistant isolates indicated multi-drug resistance to various antibiotic classes. Combinations of fosfomycin with 12 commonly used antibiotics synergistically inhibited most fosfomycin-resistant isolates. The fractional inhibitory concentration index indicated that combining fosfomycin with either aminoglycosides, glycylcyclines, fluoroquinolones, or colistin resulted in 2- to 16-fold reduction in the MIC of fosfomycin. Time-kill kinetics further confirmed the synergistic bactericidal effects of fosfomycin in combination with either amikacin, gentamicin, tobramycin, minocycline, tigecycline, or colistin, with more than 99.9% reduction in bacterial cells. Fosfomycin-based combination therapy might serve as an alternative option for the treatment of MDR A. baumannii. Further steps including in vivo efficacy and toxicity in experimental models of infection are required prior to clinical applications. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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Review

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18 pages, 1847 KiB

Open AccessEditor’s ChoiceReview

Roles of Bacterial Mechanosensitive Channels in Infection and Antibiotic Susceptibility

by Margareth Sidarta, Luna Baruah and Michaela Wenzel

Pharmaceuticals 2022, 15(7), 770; https://doi.org/10.3390/ph15070770 - 21 Jun 2022

Cited by 10 | Viewed by 3230

Abstract

Bacteria accumulate osmolytes to prevent cell dehydration during hyperosmotic stress. A sudden change to a hypotonic environment leads to a rapid water influx, causing swelling of the protoplast. To prevent cell lysis through osmotic bursting, mechanosensitive channels detect changes in turgor pressure and [...] Read more.

Bacteria accumulate osmolytes to prevent cell dehydration during hyperosmotic stress. A sudden change to a hypotonic environment leads to a rapid water influx, causing swelling of the protoplast. To prevent cell lysis through osmotic bursting, mechanosensitive channels detect changes in turgor pressure and act as emergency-release valves for the ions and osmolytes, restoring the osmotic balance. This adaptation mechanism is well-characterized with respect to the osmotic challenges bacteria face in environments such as soil or an aquatic habitat. However, mechanosensitive channels also play a role during infection, e.g., during host colonization or release into environmental reservoirs. Moreover, recent studies have proposed roles for mechanosensitive channels as determinants of antibiotic susceptibility. Interestingly, some studies suggest that they serve as entry gates for antimicrobials into cells, enhancing antibiotic efficiency, while others propose that they play a role in antibiotic-stress adaptation, reducing susceptibility to certain antimicrobials. These findings suggest different facets regarding the relevance of mechanosensitive channels during infection and antibiotic exposure as well as illustrate that they may be interesting targets for antibacterial chemotherapy. Here, we summarize the recent findings on the relevance of mechanosensitive channels for bacterial infections, including transitioning between host and environment, virulence, and susceptibility to antimicrobials, and discuss their potential as antibacterial drug targets. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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29 pages, 3495 KiB

Open AccessReview

Progress Report: Antimicrobial Drug Discovery in the Resistance Era

by Pottathil Shinu, Abdulaziz K. Al Mouslem, Anroop B. Nair, Katharigatta N. Venugopala, Mahesh Attimarad, Varsha A. Singh, Sreeharsha Nagaraja, Ghallab Alotaibi and Pran Kishore Deb

Pharmaceuticals 2022, 15(4), 413; https://doi.org/10.3390/ph15040413 - 28 Mar 2022

Cited by 15 | Viewed by 4527

Abstract

Antibiotic resistance continues to be a most serious threat to public health. This situation demands that the scientific community increase their efforts for the discovery of alternative strategies to circumvent the problems associated with conventional small molecule therapeutics. The Global Antimicrobial Resistance and [...] Read more.

Antibiotic resistance continues to be a most serious threat to public health. This situation demands that the scientific community increase their efforts for the discovery of alternative strategies to circumvent the problems associated with conventional small molecule therapeutics. The Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report (published in June 2021) discloses the rapidly increasing number of bacterial infections that are mainly caused by antimicrobial-resistant bacteria. These concerns have initiated various government agencies and other organizations to educate the public regarding the appropriate use of antibiotics. This review discusses a brief highlight on the timeline of antimicrobial drug discovery with a special emphasis on the historical development of antimicrobial resistance. In addition, new antimicrobial targets and approaches, recent developments in drug screening, design, and delivery were covered. This review also discusses the emergence and roles of various antibiotic adjuvants and combination therapies while shedding light on current challenges and future perspectives. Overall, the emergence of resistant microbial strains has challenged drug discovery but their efforts to develop alternative technologies such as nanomaterials seem to be promising for the future. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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22 pages, 710 KiB

Open AccessReview

Antibiotic Resistance in the Drinking Water: Old and New Strategies to Remove Antibiotics, Resistant Bacteria, and Resistance Genes

by Ana Catarina Duarte, Sílvia Rodrigues, Andrea Afonso, António Nogueira and Paula Coutinho

Pharmaceuticals 2022, 15(4), 393; https://doi.org/10.3390/ph15040393 - 24 Mar 2022

Cited by 19 | Viewed by 5236

Abstract

Bacterial resistance is a naturally occurring process. However, bacterial antibiotic resistance has emerged as a major public health problem in recent years. The accumulation of antibiotics in the environment, including in wastewaters and drinking water, has contributed to the development of antibiotic resistant [...] Read more.

Bacterial resistance is a naturally occurring process. However, bacterial antibiotic resistance has emerged as a major public health problem in recent years. The accumulation of antibiotics in the environment, including in wastewaters and drinking water, has contributed to the development of antibiotic resistant bacteria and the dissemination of antibiotic resistance genes (ARGs). Such can be justified by the growing consumption of antibiotics and their inadequate elimination. The conventional water treatments are ineffective in promoting the complete elimination of antibiotics and bacteria, mainly in removing ARGs. Therefore, ARGs can be horizontally transferred to other microorganisms within the aquatic environment, thus promoting the dissemination of antibiotic resistance. In this review, we discuss the efficiency of conventional water treatment processes in removing agents that can spread/stimulate the development of antibiotic resistance and the promising strategies for water remediation, mainly those based on nanotechnology and microalgae. Despite the potential of some of these approaches, the elimination of ARGs remains a challenge that requires further research. Moreover, the development of new processes must avoid the release of new contaminants for the environment, such as the chemicals resulting from nanomaterials synthesis, and consider the utilization of green and eco-friendly alternatives such as biogenic nanomaterials and microalgae-based technologies. Full article

(This article belongs to the Special Issue Mechanisms of Antibiotic Action and Resistance)

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