Comparative analysis of <i>Salmonella</i> susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network



Condell, Orla, Power, Karen A, Haendler, Kristian, Finn, Sarah, Sheridan, Aine, Sergeant, Kjell, Renaut, Jenny, Burgess, Catherine M, Hinton, Jay CD ORCID: 0000-0003-2671-6026, Nally, Jarlath E
et al (show 1 more authors) (2014) Comparative analysis of <i>Salmonella</i> susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network. FRONTIERS IN MICROBIOLOGY, 5. 373-.

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Abstract

Chlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents. We generated a Salmonella enterica serovar Typhimurium isolate (ST24(CHX)) that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defense network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defense network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism toward anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensive modifications of the same cellular processes involved in this proposed network, as well as a divergent defense response involving the up-regulation of additional targets such as the flagellar apparatus and an altered cellular phosphate metabolism. These data show that sub-lethal concentrations of chlorhexidine induce distinct changes in exposed Salmonella, and our findings provide insights into the mechanisms of action and tolerance to this biocidal agent.

Item Type: Article
Uncontrolled Keywords: Salmonella, biocide tolerance, chlorhexidine, proteomics, transcriptomics, whole genome sequencing, SNP typing
Depositing User: Symplectic Admin
Date Deposited: 17 Jul 2015 14:08
Last Modified: 05 Oct 2023 09:26
DOI: 10.3389/fmicb.2014.00373
Publisher's Statement : Copyright © 2014 Condell, Power, Händler, Finn, Sheridan, Sergeant, Renaut, Burgess, Hinton, Nally and Fanning. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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URI: https://livrepository.liverpool.ac.uk/id/eprint/2016780