scholarly journals Predicting drug resistance evolution: insights from antimicrobial peptides and antibiotics

2017 ◽  
Author(s):  
Guozhi Yu ◽  
Desiree Y Baeder ◽  
Roland R Regoes ◽  
Jens Rolff
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Antimicrobial Peptides ◽  
Lower Probability ◽  
Health Concerns ◽  
Drug Candidates ◽  
Resistance Evolution ◽  
Medical Microbiology ◽  
Evolution Of Resistance ◽  
Multicellular Organisms

AbstractAntibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides of multicellular organisms are considered part of a solution to this problem, and AMPs produced by bacteria such as colistin are last resort drugs. Importantly, antimicrobial peptides differ from many antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against antimicrobial peptides and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against antimicrobial peptides. The finding can be generalized to all drugs with pharmacodynamics similar to AMPs. Pharmacodynamic concepts are familiar to most practitioners of medical microbiology, and data can be easily obtained for any drug or drug combination. Our theoretical and conceptual framework is therefore widely applicable and can help avoid resistance evolution if implemented in antibiotic stewardship schemes or the rational choice of new drug candidates.

scholarly journals Predicting drug resistance evolution: insights from antimicrobial peptides and antibiotics

2018 ◽  
Vol 285 (1874) ◽  
pp. 20172687 ◽  
Author(s):  
Guozhi Yu ◽  
Desiree Y. Baeder ◽  
Roland R. Regoes ◽  
Jens Rolff
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Antimicrobial Peptides ◽  
Lower Probability ◽  
Health Concerns ◽  
Drug Candidates ◽  
Resistance Evolution ◽  
Medical Microbiology ◽  
Evolution Of Resistance ◽  
Multicellular Organisms

Antibiotic resistance constitutes one of the most pressing public health concerns. Antimicrobial peptides (AMPs) of multicellular organisms are considered part of a solution to this problem, and AMPs produced by bacteria such as colistin are last-resort drugs. Importantly, AMPs differ from many antibiotics in their pharmacodynamic characteristics. Here we implement these differences within a theoretical framework to predict the evolution of resistance against AMPs and compare it to antibiotic resistance. Our analysis of resistance evolution finds that pharmacodynamic differences all combine to produce a much lower probability that resistance will evolve against AMPs. The finding can be generalized to all drugs with pharmacodynamics similar to AMPs. Pharmacodynamic concepts are familiar to most practitioners of medical microbiology, and data can be easily obtained for any drug or drug combination. Our theoretical and conceptual framework is, therefore, widely applicable and can help avoid resistance evolution if implemented in antibiotic stewardship schemes or the rational choice of new drug candidates.

scholarly journals Detection of antibiotic resistance toxigenic Clostridium difficile in processed retail lettuce

2018 ◽  
Vol 2 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Yi Han ◽  
Joan King ◽  
Marlene E Janes
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Clostridium Difficile ◽  
Antimicrobial Treatment ◽  
Retail Stores ◽  
Toxin A ◽  
Toxin B ◽  
Health Concerns ◽  
Ribotype 027 ◽  
Infectious Diarrhoea

Abstract Objectives: Clostridium difficile is the major cause of infectious diarrhoea in humans after antimicrobial treatment. Clostridium difficile has been isolated from food animals and meat. The main purpose of this study was to characterize C. difficile isolated from retail lettuce and determine the antibiotic resistance using five common clinical-selected antibiotics (metronidazole, vancomycin, clindamycin, erythromycin, and cefotaxime). Materials and Methods: Lettuce samples (grown in California, Arkansas, and Louisiana) were purchased from retail stores. Results: Toxigenic C. difficile was isolated from 13.8 per cent (41/297) of the lettuce samples. Among the toxigenic isolates, only 82.9 per cent (34/41) produced toxin B, 17.1 per cent (7/41) produced both toxin A and toxin B, and two of the Louisiana C. difficile isolates were identified as ribotype 027. Under the treatment of the five antibiotics, the virulence C. difficile isolates were identified as having antibiotic resistance to metronidazole, vancomycin, and erythromycin. Conclusion: The present study reports the highest prevalence of toxigenic C. difficile in US retail lettuce. The antibiotic resistance to metronidazole, vancomycin, and erythromycin of the isolated C. difficile from retail lettuces could lead to public health concerns.

Alternative Therapies

2021 ◽  
pp. 160-182
Author(s):  
Vijay Singh Gondil ◽  
Sanjay Chhibber
Keyword(s):  
Public Health ◽  
Sustainable Development ◽  
Antibiotic Resistance ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Alternative Therapies ◽  
Alternative Strategies ◽  
Health Concerns ◽  
Near Future ◽  
Antibiotic Dose

Antibiotic resistance is one of the leading public health concerns across the globe. Antibiotics are losing their effectiveness, leading to uncertainty in available treatment options to clinicians. Resistance to antibiotics is at an all-time high, and there is a pressing demand to look for alternative antimicrobial candidates other than antibiotics. Alternative therapies include use of bacteriophages, lytic proteins, nanoparticles, phytochemicals, quorum quenchers, and other antibacterial or antivirulent agents that can eradicate bacterial infection alone or in conjunction with antibiotics. Alternative therapies can replace or lower the effective antibiotic dose, which can help to tackle antibiotic resistance as well as counter its side effects. For sustainable development of antimicrobials against drug resistant bugs, novel alternative strategies need to be explored in the near future. Alternative therapies can help researchers to construct a toolbox containing a variety of antimicrobial agents, which can be used alone, in combination with other agents, or in rotation.

scholarly journals Complete Genome Sequence of Escherichia coli Antibiotic Resistance Isolate Bank Number 0346

2021 ◽  
Vol 10 (23) ◽  
Author(s):  
Keira L. Stuart ◽  
Darrell O. Bayles ◽  
Sarah M. Shore ◽  
Tracy L. Nicholson
Keyword(s):  
Public Health ◽  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Horizontal Transfer ◽  
Complete Genome ◽  
Content Type ◽  
Health Concerns

Plasmid-mediated polymyxin resistance encoded by mcr-1 has increased public health concerns due to the potential for rapid horizontal transfer. Here, we report the complete genome sequence of colistin-resistant Escherichia coli Antibiotic Resistance Isolate Bank number 0346, harboring a plasmid-borne mcr-1 gene.

scholarly journals Effects of antibiotic resistance alleles on bacterial evolutionary responses to viral parasites

2016 ◽  
Vol 12 (5) ◽  
pp. 20160064 ◽  
Author(s):  
Flor I. Arias-Sánchez ◽  
Alex R. Hall
Keyword(s):  
Antibiotic Resistance ◽  
Population Density ◽  
Phage Resistance ◽  
Antibiotic Resistant ◽  
Relative Growth ◽  
Resistance Evolution ◽  
Mutator Allele ◽  
Evolution Of Resistance ◽  
Positive Effect ◽  
Resistant Genotypes

Antibiotic resistance has wide-ranging effects on bacterial phenotypes and evolution. However, the influence of antibiotic resistance on bacterial responses to parasitic viruses remains unclear, despite the ubiquity of such viruses in nature and current interest in therapeutic applications. We experimentally investigated this by exposing various Escherichia coli genotypes, including eight antibiotic-resistant genotypes and a mutator, to different viruses (lytic bacteriophages). Across 960 populations, we measured changes in population density and sensitivity to viruses, and tested whether variation among bacterial genotypes was explained by their relative growth in the absence of parasites, or mutation rate towards phage resistance measured by fluctuation tests for each phage. We found that antibiotic resistance had relatively weak effects on adaptation to phages, although some antibiotic-resistance alleles impeded the evolution of resistance to phages via growth costs. By contrast, a mutator allele, often found in antibiotic-resistant lineages in pathogenic populations, had a relatively large positive effect on phage-resistance evolution and population density under parasitism. This suggests costs of antibiotic resistance may modify the outcome of phage therapy against pathogenic populations previously exposed to antibiotics, but the effects of any co-occurring mutator alleles are likely to be stronger.

scholarly journals Multidrug Resistance (MDR) and Collateral Sensitivity in Bacteria, with Special Attention to Genetic and Evolutionary Aspects and to the Perspectives of Antimicrobial Peptides—A Review

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 522
Author(s):  
András Fodor ◽  
Birhan Addisie Abate ◽  
Péter Deák ◽  
László Fodor ◽  
Ervin Gyenge ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Antimicrobial Peptides ◽  
Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Mobility Patterns ◽  
Collateral Sensitivity ◽  
Resistance Evolution ◽  
Antimicrobial Peptide Resistance

Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic resistance often reduces fitness, but compensatory mutations may counteract this tendency. The appearance of new antibiotic resistance is frequently accompanied by a collateral sensitivity to other resistances. Organisms with an expanding open pan-genome, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, can withstand an increased number of resistances by exploiting their evolutionary plasticity and disseminating clonally or poly-clonally. Multidrug-resistant pathogen clones can become predominant under antibiotic stress conditions but, under the influence of negative frequency-dependent selection, are prevented from rising to dominance in a population in a commensal niche. Antimicrobial peptides have a great potential to combat multidrug resistance, since antibiotic-resistant bacteria have shown a high frequency of collateral sensitivity to antimicrobial peptides. In addition, the mobility patterns of antibiotic resistance, and antimicrobial peptide resistance, genes are completely different. The integron trade in commensal niches is fortunately limited by the species-specificity of resistance genes. Hence, we theorize that the suggested post-antibiotic era has not yet come, and indeed might never come.

scholarly journals A trimethoprim derivative impedes antibiotic resistance evolution

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Madhu Sudan Manna ◽  
Yusuf Talha Tamer ◽  
Ilona Gaszek ◽  
Nicole Poulides ◽  
Ayesha Ahmed ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistant Bacteria ◽  
Gene Encoding ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Resistance Evolution ◽  
Evolutionary Trajectories ◽  
Evolution Of Resistance

AbstractThe antibiotic trimethoprim (TMP) is used to treat a variety of Escherichia coli infections, but its efficacy is limited by the rapid emergence of TMP-resistant bacteria. Previous laboratory evolution experiments have identified resistance-conferring mutations in the gene encoding the TMP target, bacterial dihydrofolate reductase (DHFR), in particular mutation L28R. Here, we show that 4’-desmethyltrimethoprim (4’-DTMP) inhibits both DHFR and its L28R variant, and selects against the emergence of TMP-resistant bacteria that carry the L28R mutation in laboratory experiments. Furthermore, antibiotic-sensitive E. coli populations acquire antibiotic resistance at a substantially slower rate when grown in the presence of 4’-DTMP than in the presence of TMP. We find that 4’-DTMP impedes evolution of resistance by selecting against resistant genotypes with the L28R mutation and diverting genetic trajectories to other resistance-conferring DHFR mutations with catalytic deficiencies. Our results demonstrate how a detailed characterization of resistance-conferring mutations in a target enzyme can help identify potential drugs against antibiotic-resistant bacteria, which may ultimately increase long-term efficacy of antimicrobial therapies by modulating evolutionary trajectories that lead to resistance.

scholarly journals Exceptions to the rule: Why does resistance evolution not undermine antibiotic therapy in all bacterial infections?

2021 ◽  
Author(s):  
Amrita Bhattacharya ◽  
Anton Aluquin ◽  
David A Kennedy
Keyword(s):  
Public Health ◽  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Human Microbiome ◽  
Systematic Analysis ◽  
Resistance Evolution ◽  
Wide Range ◽  
Public Health Challenges

Antibiotic resistance poses one of the greatest public health challenges of the 21st century. Yet not all pathogens are equally affected by resistance evolution. Why? Here we examine what underlies variation in antibiotic resistance across human bacterial pathogens and the drugs used to treat them. We document the observed prevalence of antibiotic resistance for ′pathogen x drug′ combinations across 57 different human bacterial pathogens and 53 antibiotics from 15 drug classes used to treat them. Using AIC-based model selection we analyze 14 different traits of bacteria and antibiotics that are believed to be important in resistance evolution. Using these data, we identify the traits that best explain observed variation in resistance evolution. Our results show that nosocomial pathogens and indirectly transmitted pathogens are significantly associated with increased prevalence of resistance whereas zoonotic pathogens, specifically those with wild animal reservoirs, are associated with reduced prevalence of resistance. We found partial support for associations between drug resistance and gram classification, human microbiome reservoirs, horizontal gene transfer, and documented human-to human transfer. Global drug use, time since drug discovery, mechanism of drug action, and environmental reservoirs did not emerge as statistically robust predictors of drug resistance in our analyses. To the best of our knowledge this work is the first systematic analysis of resistance across such a wide range of human bacterial pathogens, encompassing the vast majority of common bacterial pathogens. Insights from our study may help guide public health policies and future studies on resistance control.

scholarly journals Antimicrobial peptide induced-stress renders Staphylococcus aureus susceptible to toxic nucleoside analogues

2020 ◽  
Author(s):  
Alexandro Rodríguez-Rojas ◽  
Arpita Nath ◽  
Baydaa El Shazely ◽  
Greta Santi ◽  
Joshua Jay Kim ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
Nucleotide Metabolism ◽  
Nucleoside Analogues ◽  
Antibacterial Drug ◽  
Metabolic Demand ◽  
Drug Candidates ◽  
African Clawed Frog ◽  
Multicellular Organisms ◽  
Clawed Frog

Cationic antimicrobial peptides (AMPs) are active immune effectors of multicellular organisms and also considered as new antimicrobial drug candidates. One of the problems encountered when developing AMPs as drugs is the difficulty to reach sufficient killing concentrations under physiological conditions. Here, using pexiganan, a cationic peptide derived from a host defence peptide of the African clawed frog and the first AMP developed into an antibacterial drug, we studied if sub-lethal effects of AMPs can be harnessed to devise treatment combinations. We studied the pexiganan stress response of Staphylococcus aureus at sub-lethal concentrations using quantitative proteomics. Several proteins involved in nucleotide metabolism were elevated, suggesting a metabolic demand. We then show that S. aureus is highly susceptible to antimetabolite nucleoside analogues when exposed to pexiganan, even at sub-inhibitory concentrations. These findings could be used to enhance pexiganan potency while decreasing the risk of resistance emergence, and our findings can likely be extended to other antimicrobial peptides.

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