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Comparison of gene expression profiles of uropathogenic Escherichia coli CFT073 after prolonged exposure to subinhibitory concentrations of different biocides

ABSTRACT: Biocides are chemical compounds widely used in hospital settings for a variety of purposes, but mainly for disinfection. The chemical properties of a biocide, as well as the biocide concentration, influence which cellular targets are affected. Exposure of bacteria to residual concentrations of biocides could lead to development of increased resistance towards the biocide in use, as well as cross-resistance towards other antimicrobials, including antibiotics. The aim of this study was to examine whether biocides could induce any potentially relevant genes that could affect pathogen's drug resistance or fitness. By examining global gene expression of the uropathogenic Escherichia coli CFT073 after exposure to subinhibitory concentrations of four biocides (benzalkonium chloride - BAC, chlorhexidine - CHX, hydrogen peroxide - H2O2, triclosan - TSN), we found that each biocide changed expression of different groups of genes and that exposure to benzalkonum chloride caused changes in expression of the largest number of genes among all biocides. In general, the four biocides tested in this study at subinhibitory concentrations did not increase the resistance potential of the pathogen to other antimicrobials. We could, however, identify clusters of genes that could possibly help the strain to grow in the presence of a biocide in the medium.

ORGANISM(S): Escherichia coli Escherichia coli CFT073

PROVIDER: GSE135556 | GEO | 2019/12/05

REPOSITORIES: GEO

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Project description:Subinhibitory concentrations of the neuroleptic drug thioridazine (TDZ) are well-known to enhance the killing of methicillin-resistant S. aureus (MRSA) by Î²-lactam antibiotics, however, the mechanism underlying the synergy between TDZ and Î²-lactams is not fully understood. In the present study we have examined the effect of a subinhibitory concentration of TDZ on antimicrobial resistance, the global transcriptome, and the cell wall composition of MRSA USA300. We show that TDZ is able to sensitize the bacteria to several classes of antimicrobials targeting the late stages of peptidoglycan synthesis. Furthermore, our microarray analysis demonstrates that TDZ modulates the expression of genes encoding membrane and surface proteins, transporters, and enzymes involved in amino acid biosynthesis. Interestingly, resemblance between the transcriptional profile of TDZ treatment and the transcriptomic response of S. aureus to known inhibitors of cell wall synthesis suggests that TDZ disturbs peptidoglycan biosynthesis at a stage that precedes transpeptidation. In support of this notion, dramatic changes in the muropeptide profile of USA300 were observed following growth in the presence of TDZ, indicating that TDZ can interfere with the formation of the pentaglycine branches. Strikingly, the addition of glycine to the growth medium relieved the effect of TDZ on the muropeptide profile. Furthermore, exogenous glycine offered a modest protective effect against TDZ-induced Î²-lactam sensitivity. We propose that TDZ exposure leads to a shortage of intracellular amino acids, including glycine, which is required for the production of normal peptidoglycan precursors with pentaglycine branches, the correct substrate of S. aureus penicillin-binding proteins. Collectively, this work demonstrates that TDZ has a major impact on the cell wall biosynthesis pathway in S. aureus and provides new insights into how MRSA may be sensitized towards Î²-lactam antibiotics. Staphylococcus aureus USA300 was grown to early exponential phase and treated with TDZ (16 Âµg/ml) alone or in combination with DCX (0.125 Âµg/ml) for 30 min. Changes in global gene expression were analyzed using the untreated culture as control. Hybridizations were performed in triplicate using RNA isolated from independent cultures.

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Comparison of gene expression profiles of uropathogenic Escherichia coli CFT073 after prolonged exposure to subinhibitory concentrations of different biocides

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