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Implications of stress-induced genetic variation for minimizing multidrug resistance in bacteria.

ABSTRACT: BACKGROUND: Antibiotic resistance in bacterial infections is a growing threat to public health. Recent evidence shows that when exposed to stressful conditions, some bacteria perform higher rates of horizontal gene transfer and mutation, and thus acquire antibiotic resistance more rapidly. METHODS: We incorporate this new notion into a mathematical model for the emergence of antibiotic multi-resistance in a hospital setting. RESULTS: We show that when stress has a considerable effect on genetic variation, the emergence of antibiotic resistance is dramatically affected. A strategy in which patients receive a combination of antibiotics (combining) is expected to facilitate the emergence of multi-resistant bacteria when genetic variation is stress-induced. The preference between a strategy in which one of two effective drugs is assigned randomly to each patient (mixing), and a strategy where only one drug is administered for a specific period of time (cycling) is determined by the resistance acquisition mechanisms. We discuss several features of the mechanisms by which stress affects variation and predict the conditions for success of different antibiotic treatment strategies. CONCLUSIONS: These findings should encourage research on the mechanisms of stress-induced genetic variation and establish the importance of incorporating data about these mechanisms when considering antibiotic treatment strategies.

SUBMITTER: Obolski U

PROVIDER: S-EPMC3482572 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Implications of stress-induced genetic variation for minimizing multidrug resistance in bacteria.

Obolski Uri U Hadany Lilach L

BMC medicine 20120813

<h4>Background</h4>Antibiotic resistance in bacterial infections is a growing threat to public health. Recent evidence shows that when exposed to stressful conditions, some bacteria perform higher rates of horizontal gene transfer and mutation, and thus acquire antibiotic resistance more rapidly.<h4>Methods</h4>We incorporate this new notion into a mathematical model for the emergence of antibiotic multi-resistance in a hospital setting.<h4>Results</h4>We show that when stress has a considerable ...[more]

PMID: 22889082

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Project description:BackgroundTetR-family transcriptional regulators (TFTRs) are DNA binding factors that regulate gene expression in bacteria. Well-studied TFTRs, such as AcrR, which regulates efflux pump expression, are usually encoded alongside target operons. Recently, it has emerged that there are many TFTRs which act as global multi-target regulators. Our classical view of TFTRs as simple, single-target regulators therefore needs to be reconsidered. As some TFTRs regulate essential processes (e.g. metabolism) or processes which are important determinants of resistance and virulence (e.g. biofilm formation and efflux gene expression) and as TFTRs are present throughout pathogenic bacteria, they may be good drug discovery targets for tackling antimicrobial resistant infections. However, the prevalence and conservation of individual TFTR genes in Gram-negative species, has to our knowledge, not yet been studied.ResultsHere, a wide-scale search for TFTRs in available proteomes of clinically relevant pathogens Salmonella and Escherichia species was performed and these regulators further characterised. The majority of identified TFTRs are involved in efflux regulation in both Escherichia and Salmonella. The percentage variance in TFTR genes of these genera was found to be higher in those regulating genes involved in efflux, bleach survival or biofilm formation than those regulating more constrained processes. Some TFTRs were found to be present in all strains and species of these two genera, whereas others (i.e. TetR) are only present in some strains and some (i.e. RamR) are genera-specific. Two further pathogens on the WHO priority pathogen list (K. pneumoniae and P. aeruginosa) were then searched for the presence of the TFTRs conserved in Escherichia and Salmonella.ConclusionsThrough bioinformatics and literature analyses, we present that TFTRs are a varied and heterogeneous family of proteins required for the regulation of numerous important processes, with consequences to antimicrobial resistance and virulence, and that the roles and responses of these proteins are frequently underestimated.

Dataset Information

Implications of stress-induced genetic variation for minimizing multidrug resistance in bacteria.

Publications

Implications of stress-induced genetic variation for minimizing multidrug resistance in bacteria.

Similar Datasets

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