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

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    Author
    Condell, Orla
    Power, Karen A.
    Handler, Kristian
    Finn, Sarah
    Sheridan, Aine
    Sergeant, Kjell
    Renaut, Jenny
    Burgess, Catherine cc
    Hinton, Jay C.D.
    Nally, Jarlath E.
    Fanning, Seamus
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    Keyword
    Salmonella
    Biocide tolerance
    Chlorhexidine
    Proteomics
    Transcriptomics
    Whole genome sequencing
    SNP typing
    Date
    2014-08-01
    
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    URI
    http://hdl.handle.net/11019/803
    Citation
    Condell O, Power KA, Händler K, Finn S, Sheridan A, Sergeant K, Renaut J, Burgess CM, Hinton JCD, Nally JE and Fanning S (2014) Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network. Front. Microbiol. 5:373. doi: 10.3389/fmicb.2014.00373
    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 (ST24CHX) 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.
    Funder
    Department of Agriculture, Food and the Marine, Ireland
    Grant Number
    08/RD/TAFRC/616
    ae974a485f413a2113503eed53cd6c53
    http://dx.doi.org/10.3389/fmicb.2014.00373
    Scopus Count
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    Food Safety

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