# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4395 | 0 | 1.0000 | Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Epidemics of drug-resistant bacteria emerge worldwide, even as resistant strains frequently have reduced fitness compared to their drug-susceptible counterparts. Data from model systems suggest that the fitness cost of antimicrobial resistance can be reduced by compensatory mutations; however, there is limited evidence that compensatory evolution has any significant role in the success of drug-resistant bacteria in human populations. Here we describe a set of compensatory mutations in the RNA polymerase genes of rifampicin-resistant M. tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harboring these compensatory mutations showed a high competitive fitness in vitro. Moreover, these mutations were associated with high fitness in vivo, as determined by examining their relative clinical frequency across patient populations. Of note, in countries with the world's highest incidence of multidrug-resistant (MDR) TB, more than 30% of MDR clinical isolates had this form of mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR TB. | 2011 | 22179134 |
| 4396 | 1 | 0.9999 | Insights into the processes that drive the evolution of drug resistance in Mycobacterium tuberculosis. At present, the successful transmission of drug-resistant Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, in human populations, threatens tuberculosis control worldwide. Differently from many other bacteria, M. tuberculosis drug resistance is acquired mainly through mutations in specific drug resistance-associated genes. The panel of mutations is highly diverse, but depends on the affected gene and M. tuberculosis genetic background. The variety of genetic profiles observed in drug-resistant clinical isolates underlines different evolutionary trajectories towards multiple drug resistance, although some mutation patterns are prominent. This review discusses the intrinsic processes that may influence drug resistance evolution in M. tuberculosis, such as mutation rate, drug resistance-associated mutations, fitness cost, compensatory mutations and epistasis. This knowledge should help to better predict the risk of emergence of highly resistant M. tuberculosis strains and to develop new tools and strategies to limit the development and spread of MDR and XDR strains. | 2018 | 30344622 |
| 4394 | 2 | 0.9999 | Signatures of Selection at Drug Resistance Loci in Mycobacterium tuberculosis. Tuberculosis (TB) is the leading cause of death by an infectious disease, and global TB control efforts are increasingly threatened by drug resistance in Mycobacterium tuberculosis. Unlike most bacteria, where lateral gene transfer is an important mechanism of resistance acquisition, resistant M. tuberculosis arises solely by de novo chromosomal mutation. Using whole-genome sequencing data from two natural populations of M. tuberculosis, we characterized the population genetics of known drug resistance loci using measures of diversity, population differentiation, and convergent evolution. We found resistant subpopulations to be less diverse than susceptible subpopulations, consistent with ongoing transmission of resistant M. tuberculosis. A subset of resistance genes ("sloppy targets") were characterized by high diversity and multiple rare variants; we posit that a large genetic target for resistance and relaxation of purifying selection contribute to high diversity at these loci. For "tight targets" of selection, the path to resistance appeared narrower, evidenced by single favored mutations that arose numerous times in the phylogeny and segregated at markedly different frequencies in resistant and susceptible subpopulations. These results suggest that diverse genetic architectures underlie drug resistance in M. tuberculosis and that combined approaches are needed to identify causal mutations. Extrapolating from patterns observed for well-characterized genes, we identified novel candidate variants involved in resistance. The approach outlined here can be extended to identify resistance variants for new drugs, to investigate the genetic architecture of resistance, and when phenotypic data are available, to find candidate genetic loci underlying other positively selected traits in clonal bacteria. IMPORTANCEMycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a significant burden on global health. Antibiotic treatment imposes strong selective pressure on M. tuberculosis populations. Identifying the mutations that cause drug resistance in M. tuberculosis is important for guiding TB treatment and halting the spread of drug resistance. Whole-genome sequencing (WGS) of M. tuberculosis isolates can be used to identify novel mutations mediating drug resistance and to predict resistance patterns faster than traditional methods of drug susceptibility testing. We have used WGS from natural populations of drug-resistant M. tuberculosis to characterize effects of selection for advantageous mutations on patterns of diversity at genes involved in drug resistance. The methods developed here can be used to identify novel advantageous mutations, including new resistance loci, in M. tuberculosis and other clonal pathogens. | 2018 | 29404424 |
| 9922 | 3 | 0.9999 | De novo acquisition of antibiotic resistance in six species of bacteria. Bacteria can become resistant to antibiotics in two ways: by acquiring resistance genes through horizontal gene transfer and by de novo development of resistance upon exposure to non-lethal concentrations. The importance of the second process, de novo build-up, has not been investigated systematically over a range of species and may be underestimated as a result. To investigate the DNA mutation patterns accompanying the de novo antibiotic resistance acquisition process, six bacterial species encountered in the food chain were exposed to step-wise increasing sublethal concentrations of six antibiotics to develop high levels of resistance. Phenotypic and mutational landscapes were constructed based on whole-genome sequencing at two time points of the evolutionary trajectory. In this study, we found that (1) all of the six strains can develop high levels of resistance against most antibiotics; (2) increased resistance is accompanied by different mutations for each bacterium-antibiotic combination; (3) the number of mutations varies widely, with Y. enterocolitica having by far the most; (4) in the case of fluoroquinolone resistance, a mutational pattern of gyrA combined with parC is conserved in five of six species; and (5) mutations in genes coding for efflux pumps are widely encountered in gram-negative species. The overall conclusion is that very similar phenotypic outcomes are instigated by very different genetic changes. The outcome of this study may assist policymakers when formulating practical strategies to prevent development of antimicrobial resistance in human and veterinary health care.IMPORTANCEMost studies on de novo development of antimicrobial resistance have been performed on Escherichia coli. To examine whether the conclusions of this research can be applied to more bacterial species, six species of veterinary importance were made resistant to six antibiotics, each of a different class. The rapid build-up of resistance observed in all six species upon exposure to non-lethal concentrations of antimicrobials indicates a similar ability to adjust to the presence of antibiotics. The large differences in the number of DNA mutations accompanying de novo resistance suggest that the mechanisms and pathways involved may differ. Hence, very similar phenotypes can be the result of various genotypes. The implications of the outcome are to be considered by policymakers in the area of veterinary and human healthcare. | 2025 | 39907470 |
| 8932 | 4 | 0.9999 | Alternative Evolutionary Paths to Bacterial Antibiotic Resistance Cause Distinct Collateral Effects. When bacteria evolve resistance against a particular antibiotic, they may simultaneously gain increased sensitivity against a second one. Such collateral sensitivity may be exploited to develop novel, sustainable antibiotic treatment strategies aimed at containing the current, dramatic spread of drug resistance. To date, the presence and molecular basis of collateral sensitivity has only been studied in few bacterial species and is unknown for opportunistic human pathogens such as Pseudomonas aeruginosa. In the present study, we assessed patterns of collateral effects by experimentally evolving 160 independent populations of P. aeruginosa to high levels of resistance against eight commonly used antibiotics. The bacteria evolved resistance rapidly and expressed both collateral sensitivity and cross-resistance. The pattern of such collateral effects differed to those previously reported for other bacterial species, suggesting interspecific differences in the underlying evolutionary trade-offs. Intriguingly, we also identified contrasting patterns of collateral sensitivity and cross-resistance among the replicate populations adapted to the same drug. Whole-genome sequencing of 81 independently evolved populations revealed distinct evolutionary paths of resistance to the selective drug, which determined whether bacteria became cross-resistant or collaterally sensitive towards others. Based on genomic and functional genetic analysis, we demonstrate that collateral sensitivity can result from resistance mutations in regulatory genes such as nalC or mexZ, which mediate aminoglycoside sensitivity in β-lactam-adapted populations, or the two-component regulatory system gene pmrB, which enhances penicillin sensitivity in gentamicin-resistant populations. Our findings highlight substantial variation in the evolved collateral effects among replicates, which in turn determine their potential in antibiotic therapy. | 2017 | 28541480 |
| 4393 | 5 | 0.9998 | Mechanisms of Staphylococcus aureus Antibiotics Resistance Revealed by Adaptive Laboratory Evolution. Infection caused by drug-resistant Staphylococcus aureus is a serious public health and veterinary concern. Lack of a comprehensive understanding of the mechanisms underlying the emergence of drug-resistant strains, it makes S. aureus one of the most intractable pathogenic bacteria. To identify mutations that confer resistance to anti-S. aureus drugs, we established a laboratory-based adaptive evolution system and performed 10 rounds of evolution experiments against 15 clinically used antibiotics. We discovered a panel of known and novel resistance-associated sites after performing whole-genome sequencing. Furthermore, we found that the resistance evolved at distinct rates. For example, streptomycin, rifampicin, fusidic acid and novobiocin all developed significant resistance quickly in the second round of evolution. Intriguingly, the cross-resistance experiment reveals that nearly all drug-resistant strains have varying degrees of increased sensitivity to fusidic acid, pointing to a novel approach to battle AMR. In addition, the in silico docking analysis shows that the evolved mutants affect the interaction of rifampcin-rpoB, as well as the novobiocin-gyrB. Moreover, for the genes we got in the laboratory evolution, mutant genes of clinical isolates of human had significant differences from the environmental isolates and animal isolates. We believe that the strategy and data set in this research will be helpful for battling AMR issue of S. aureus, and adaptable to other pathogenic microbes. | 2025 | 39762552 |
| 4263 | 6 | 0.9998 | The emergence of antibiotic resistance by mutation. The emergence of mutations in nucleic acids is one of the major factors underlying evolution, providing the working material for natural selection. Most bacteria are haploid for the vast majority of their genes and, coupled with typically short generation times, this allows mutations to emerge and accumulate rapidly, and to effect significant phenotypic changes in what is perceived to be real-time. Not least among these phenotypic changes are those associated with antibiotic resistance. Mechanisms of horizontal gene spread among bacterial strains or species are often considered to be the main mediators of antibiotic resistance. However, mutational resistance has been invaluable in studies of bacterial genetics, and also has primary clinical importance in certain bacterial species, such as Mycobacterium tuberculosis and Helicobacter pylori, or when considering resistance to particular antibiotics, especially to synthetic agents such as fluoroquinolones and oxazolidinones. In addition, mutation is essential for the continued evolution of acquired resistance genes and has, e.g., given rise to over 100 variants of the TEM family of beta-lactamases. Hypermutator strains of bacteria, which have mutations in genes affecting DNA repair and replication fidelity, have elevated mutation rates. Mutational resistance emerges de novo more readily in these hypermutable strains, and they also provide a suitable host background for the evolution of acquired resistance genes in vitro. In the clinical setting, hypermutator strains of Pseudomonas aeruginosa have been isolated from the lungs of cystic fibrosis patients, but a more general role for hypermutators in the emergence of clinically relevant antibiotic resistance in a wider variety of bacterial pathogens has not yet been proven. | 2007 | 17184282 |
| 4264 | 7 | 0.9998 | Mutational Evolution of Pseudomonas aeruginosa Resistance to Ribosome-Targeting Antibiotics. The present work examines the evolutionary trajectories of replicate Pseudomonas aeruginosa cultures in presence of the ribosome-targeting antibiotics tobramycin and tigecycline. It is known that large number of mutations across different genes - and therefore a large number of potential pathways - may be involved in resistance to any single antibiotic. Thus, evolution toward resistance might, to a large degree, rely on stochasticity, which might preclude the use of predictive strategies for fighting antibiotic resistance. However, the present results show that P. aeruginosa populations evolving in parallel in the presence of antibiotics (either tobramycin or tigecycline) follow a set of trajectories that present common elements. In addition, the pattern of resistance mutations involved include common elements for these two ribosome-targeting antimicrobials. This indicates that mutational evolution toward resistance (and perhaps other properties) is to a certain degree deterministic and, consequently, predictable. These findings are of interest, not just for P. aeruginosa, but in understanding the general rules involved in the evolution of antibiotic resistance also. In addition, the results indicate that bacteria can evolve toward higher levels of resistance to antibiotics against which they are considered to be intrinsically resistant, as tigecycline in the case of P. aeruginosa and that this may confer cross-resistance to other antibiotics of therapeutic value. Our results are particularly relevant in the case of patients under empiric treatment with tigecycline, which frequently suffer P. aeruginosa superinfections. | 2018 | 30405685 |
| 8931 | 8 | 0.9998 | Limited Evolutionary Conservation of the Phenotypic Effects of Antibiotic Resistance Mutations. Multidrug-resistant clinical isolates are common in certain pathogens, but rare in others. This pattern may be due to the fact that mutations shaping resistance have species-specific effects. To investigate this issue, we transferred a range of resistance-conferring mutations and a full resistance gene into Escherichia coli and closely related bacteria. We found that resistance mutations in one bacterial species frequently provide no resistance, in fact even yielding drug hypersensitivity in close relatives. In depth analysis of a key gene involved in aminoglycoside resistance (trkH) indicated that preexisting mutations in other genes-intergenic epistasis-underlie such extreme differences in mutational effects between species. Finally, reconstruction of adaptive landscapes under multiple antibiotic stresses revealed that mutations frequently provide multidrug resistance or elevated drug susceptibility (i.e., collateral sensitivity) only with certain combinations of other resistance mutations. We conclude that resistance and collateral sensitivity are contingent upon the genetic makeup of the bacterial population, and such contingency could shape the long-term fate of resistant bacteria. These results underlie the importance of species-specific treatment strategies. | 2019 | 31058961 |
| 4392 | 9 | 0.9998 | The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem. The airborne pathogen Mycobacterium tuberculosis is responsible for a present major public health problem worsened by the emergence of drug resistance. M. tuberculosis has acquired and developed streptomycin (STR) resistance mechanisms that have been maintained and transmitted in the population over the last decades. Indeed, STR resistant mutations are frequently identified across the main M. tuberculosis lineages that cause tuberculosis outbreaks worldwide. The spread of STR resistance is likely related to the low impact of the most frequent underlying mutations on the fitness of the bacteria. The withdrawal of STR from the first-line treatment of tuberculosis potentially lowered the importance of studying STR resistance. However, the prevalence of STR resistance remains very high, could be underestimated by current genotypic methods, and was found in outbreaks of multi-drug (MDR) and extensively drug (XDR) strains in different geographic regions. Therefore, the contribution of STR resistance to the problem of tuberculosis drug resistance should not be neglected. Here, we review the impact of STR resistance and detail well-known and novel candidate STR resistance mechanisms, genes, and mutations. In addition, we aim to provide insights into the possible role of STR resistance in the development of multi-drug resistant tuberculosis. | 2021 | 34946952 |
| 4262 | 10 | 0.9998 | Fitness cost of antibiotic susceptibility during bacterial infection. Advances in high-throughput DNA sequencing allow for a comprehensive analysis of bacterial genes that contribute to virulence in a specific infectious setting. Such information can yield new insights that affect decisions on how to best manage major public health issues such as the threat posed by increasing antimicrobial drug resistance. Much of the focus has been on the consequences of the selective advantage conferred on drug-resistant strains during antibiotic therapy. It is thought that the genetic and phenotypic changes that confer resistance also result in concomitant reductions in in vivo fitness, virulence, and transmission. However, experimental validation of this accepted paradigm is modest. Using a saturated transposon library of Pseudomonas aeruginosa, we identified genes across many functional categories and operons that contributed to maximal in vivo fitness during lung infections in animal models. Genes that bestowed both intrinsic and acquired antibiotic resistance provided a positive in vivo fitness advantage to P. aeruginosa during infection. We confirmed these findings in the pathogenic bacteria Acinetobacter baumannii and Vibrio cholerae using murine and rabbit infection models, respectively. Our results show that efforts to confront the worldwide increase in antibiotic resistance might be exacerbated by fitness advantages that enhance virulence in drug-resistant microbes. | 2015 | 26203082 |
| 3808 | 11 | 0.9998 | Expression Profiling of Antibiotic-Resistant Bacteria Obtained by Laboratory Evolution. To elucidate the mechanisms of antibiotic resistance, integrating phenotypic and genotypic features in resistant strains is important. Here, we describe the expression profiling of antibiotic-resistant Escherichia coli strains obtained by laboratory evolution, and a method for extracting a small number of genes whose expression changes can contribute to the acquisition of resistance. | 2017 | 27873258 |
| 6267 | 12 | 0.9998 | Beta-lactamase dependent and independent evolutionary paths to high-level ampicillin resistance. The incidence of beta-lactam resistance among clinical isolates is a major health concern. A key method to study the emergence of antibiotic resistance is adaptive laboratory evolution. However, in the case of the beta-lactam ampicillin, bacteria evolved in laboratory settings do not recapitulate clinical-like resistance levels, hindering efforts to identify major evolutionary paths and their dependency on genetic background. Here, we used the Microbial Evolution and Growth Arena (MEGA) plate to select ampicillin-resistant Escherichia coli mutants with varying degrees of resistance. Whole-genome sequencing of resistant isolates revealed that ampicillin resistance was acquired via a combination of single-point mutations and amplification of the gene encoding beta-lactamase AmpC. However, blocking AmpC-mediated resistance revealed latent adaptive pathways: strains deleted for ampC were able to adapt through combinations of changes in genes involved in multidrug resistance encoding efflux pumps, transcriptional regulators, and porins. Our results reveal that combinations of distinct genetic mutations, accessible at large population sizes, can drive high-level resistance to ampicillin even independently of beta-lactamases. | 2024 | 38918379 |
| 3829 | 13 | 0.9998 | Associations among Antibiotic and Phage Resistance Phenotypes in Natural and Clinical Escherichia coli Isolates. The spread of antibiotic resistance is driving interest in new approaches to control bacterial pathogens. This includes applying multiple antibiotics strategically, using bacteriophages against antibiotic-resistant bacteria, and combining both types of antibacterial agents. All these approaches rely on or are impacted by associations among resistance phenotypes (where bacteria resistant to one antibacterial agent are also relatively susceptible or resistant to others). Experiments with laboratory strains have shown strong associations between some resistance phenotypes, but we lack a quantitative understanding of associations among antibiotic and phage resistance phenotypes in natural and clinical populations. To address this, we measured resistance to various antibiotics and bacteriophages for 94 natural and clinical Escherichia coli isolates. We found several positive associations between resistance phenotypes across isolates. Associations were on average stronger for antibacterial agents of the same type (antibiotic-antibiotic or phage-phage) than different types (antibiotic-phage). Plasmid profiles and genetic knockouts suggested that such associations can result from both colocalization of resistance genes and pleiotropic effects of individual resistance mechanisms, including one case of antibiotic-phage cross-resistance. Antibiotic resistance was predicted by core genome phylogeny and plasmid profile, but phage resistance was predicted only by core genome phylogeny. Finally, we used observed associations to predict genes involved in a previously uncharacterized phage resistance mechanism, which we verified using experimental evolution. Our data suggest that susceptibility to phages and antibiotics are evolving largely independently, and unlike in experiments with lab strains, negative associations between antibiotic resistance phenotypes in nature are rare. This is relevant for treatment scenarios where bacteria encounter multiple antibacterial agents.IMPORTANCE Rising antibiotic resistance is making it harder to treat bacterial infections. Whether resistance to a given antibiotic spreads or declines is influenced by whether it is associated with altered susceptibility to other antibiotics or other stressors that bacteria encounter in nature, such as bacteriophages (viruses that infect bacteria). We used natural and clinical isolates of Escherichia coli, an abundant species and key pathogen, to characterize associations among resistance phenotypes to various antibiotics and bacteriophages. We found associations between some resistance phenotypes, and in contrast to past work with laboratory strains, they were exclusively positive. Analysis of bacterial genome sequences and horizontally transferred genetic elements (plasmids) helped to explain this, as well as our finding that there was no overall association between antibiotic resistance and bacteriophage resistance profiles across isolates. This improves our understanding of resistance evolution in nature, potentially informing new rational therapies that combine different antibacterials, including bacteriophages. | 2017 | 29089428 |
| 9897 | 14 | 0.9998 | The fitness connection of antibiotic resistance. More than three decades ago multidrug-resistant (MDR) clones of the pathogens: Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Clostridioides difficile, Enterococcus faecium, Pseudomonas aeruginosa and Acinetobacter baumannii have started to disseminate across wide geographical areas. A characteristic feature of all these MDR lineages is the carriage of some mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase and topoisomerase IV which besides conferring resistance to fluoroquinolones are associated with a fitness benefit. Several lines of evidence strongly suggest that extra fitness conferred by these mutations facilitated the dissemination of the international MDR lineages. MDR pathogens require extra energy to cover the fitness cost conferred by the excess antibiotic resistance gene cargo. However, extra energy generated by upgraded metabolic activity was demonstrated to increase the uptake of antibiotics enhancing susceptibility. Accordingly, MDR bacteria need additional positive fitness schemes which, similarly to the QRDR advantage, will not compromise resistance. Some of these, not clone-specific effects are large genomes, the carriage of low-cost plasmids, the transfer of plasmid genes to the chromosome, the application of weak promoters in integrons and various techniques for the economic control of the activity of the integrase enzyme including a highly sophisticated system in A. baumannii. These impacts - among others - will confer a fitness advantage promoting the spread of MDR pathogens. However, even the potential of extra fitness generated by the combined effect of various schemes is not without limit and virulence-related genes or less relevant antibiotic resistance gene cargoes will often be sacrificed to permit the acquisition of high-priority resistance determinants. Accordingly major MDR clone strains are usually less virulent than susceptible isolates. In summary, a fitness approach to the research of antibiotic resistance is very useful since the fitness status of MDR bacteria seem to profoundly impact the capacity to disseminate in the healthcare setting. | 2025 | 40276228 |
| 3836 | 15 | 0.9998 | Bacterial recombination promotes the evolution of multi-drug-resistance in functionally diverse populations. Bacterial recombination is believed to be a major factor explaining the prevalence of multi-drug-resistance (MDR) among pathogenic bacteria. Despite extensive evidence for exchange of resistance genes from retrospective sequence analyses, experimental evidence for the evolutionary benefits of bacterial recombination is scarce. We compared the evolution of MDR between populations of Acinetobacter baylyi in which we manipulated both the recombination rate and the initial diversity of strains with resistance to single drugs. In populations lacking recombination, the initial presence of multiple strains resistant to different antibiotics inhibits the evolution of MDR. However, in populations with recombination, the inhibitory effect of standing diversity is alleviated and MDR evolves rapidly. Moreover, only the presence of DNA harbouring resistance genes promotes the evolution of resistance, ruling out other proposed benefits for recombination. Together, these results provide direct evidence for the fitness benefits of bacterial recombination and show that this occurs by mitigation of functional interference between genotypes resistant to single antibiotics. Although analogous to previously described mechanisms of clonal interference among alternative beneficial mutations, our results actually highlight a different mechanism by which interactions among co-occurring strains determine the benefits of recombination for bacterial evolution. | 2012 | 22048956 |
| 8857 | 16 | 0.9998 | Colistin-phage combinations decrease antibiotic resistance in Acinetobacter baumannii via changes in envelope architecture. Multidrug-resistant bacterial infections are becoming increasingly common, with only few last-resort antibiotics such as colistin available for clinical therapy. An alternative therapeutic strategy gaining momentum is phage therapy, which has the advantage of not being affected by bacterial resistance to antibiotics. However, a major challenge in phage therapy is the rapid emergence of phage-resistant bacteria. In this work, our main aim was to understand the mechanisms of phage-resistance used by the top priority pathogen Acinetobacter baumannii. We isolated the novel phage Phab24, capable of infecting colistin-sensitive and -resistant strains of A. baumannii. After co-incubating Phab24 with its hosts, we obtained phage-resistant mutants which were characterized on both genotypic and phenotypic levels. Using whole genome sequencing, we identified phage-resistant strains that displayed mutations in genes that alter the architecture of the bacterial envelope at two levels: the capsule and the outer membrane. Using an adsorption assay, we confirmed that phage Phab24 uses the bacterial capsule as its primary receptor, with the outer membrane possibly serving as the secondary receptor. Interestingly, the phage-resistant isolates were less virulent compared to the parental strains in a Galleria mellonella infection model. Most importantly, we observed that phage-resistant bacteria that evolved in the absence of antibiotics exhibited an increased sensitivity to colistin, even though the antibiotic resistance mechanism per se remained unaltered. This increase in antibiotic sensitivity is a direct consequence of the phage-resistance mechanism, and could potentially be exploited in the clinical setting. | 2021 | 34736365 |
| 4833 | 17 | 0.9998 | Emerging mechanisms of fluoroquinolone resistance. Broad use of fluoroquinolones has been followed by emergence of resistance, which has been due mainly to chromosomal mutations in genes encoding the subunits of the drugs' target enzymes, DNA gyrase and topoisomerase IV, and in genes that affect the expression of diffusion channels in the outer membrane and multidrug-resistance efflux systems. Resistance emerged first in species in which single mutations were sufficient to cause clinically important levels of resistance (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). Subsequently, however, resistance has emerged in bacteria such as Campylobacter jejuni, Escherichia coli, and Neisseria gonorrhoeae, in which multiple mutations are required to generate clinically important resistance. In these circumstances, the additional epidemiologic factors of drug use in animals and human-to-human spread appear to have contributed. Resistance in Streptococcus pneumoniae, which is currently low, will require close monitoring as fluoroquinolones are used more extensively for treating respiratory tract infections. | 2001 | 11294736 |
| 4391 | 18 | 0.9998 | 'To be, or not to be'-The dilemma of 'silent' antimicrobial resistance genes in bacteria. Antimicrobial resistance is a serious threat to public health that dramatically undermines our ability to treat bacterial infections. Microorganisms exhibit resistance to different drug classes by acquiring resistance determinants through multiple mechanisms including horizontal gene transfer. The presence of drug resistance genotypes is mostly associated with corresponding phenotypic resistance against the particular antibiotic. However, bacterial communities harbouring silent antimicrobial resistance genes-genes whose presence is not associated with a corresponding resistant phenotype do exist. Under suitable conditions, the expression pattern of such genes often revert and regain resistance and could potentially lead to therapeutic failure. We often miss the presence of silent genes, since the current experimental paradigms are focused on resistant strains. Therefore, the knowledge on the prevalence, importance and mechanism of silent antibiotic resistance genes in bacterial pathogens are very limited. Silent genes, therefore, provide an additional level of complexity in the war against drug-resistant bacteria, reminding us that not only phenotypically resistant strains but also susceptible strains should be carefully investigated. In this review, we discuss the presence of silent antimicrobial resistance genes in bacteria, their relevance and their importance in public health. | 2022 | 35882476 |
| 4422 | 19 | 0.9998 | Diversity among multidrug-resistant enterococci. Enterococci are associated with both community- and hospital-acquired infections. Even though they do not cause severe systemic inflammatory responses, such as septic shock, enterococci present a therapeutic challenge because of their resistance to a vast array of antimicrobial drugs, including cell-wall active agents, all commercially available aminoglycosides, penicillin and ampicillin, and vancomycin. The combination of the latter two occurs disproportionately in strains resistant to many other antimicrobial drugs. The propensity of enterococci to acquire resistance may relate to their ability to participate in various forms of conjugation, which can result in the spread of genes as part of conjugative transposons, pheromone-responsive plasmids, or broad host-range plasmids. Enterococcal hardiness likely adds to resistance by facilitating survival in the environment (and thus enhancing potential spread from person to person) of a multidrug-resistant clone. The combination of these attributes within the genus Enterococcus suggests that these bacteria and their resistance to antimicrobial drugs will continue to pose a challenge. | 1998 | 9452397 |