Reduced Susceptibility to Antiseptics Is Conferred by Heterologous Housekeeping Genes

Tansirichaiya, Supathep, Reynolds, Liam J., Cristarella, Gianmarco, Wong, Li Chin, Rosendahl, Kimie and Roberts, Adam ORCID: https://orcid.org/0000-0002-0760-3088 (2018) 'Reduced Susceptibility to Antiseptics Is Conferred by Heterologous Housekeeping Genes'. Microbial Drug Resistance, Vol 24, Issue 2, pp. 105-112.

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Abstract

Antimicrobial resistance is common in the microbial inhabitants of the human oral cavity. Antimicrobials are commonly encountered by oral microbes as they are present in our diet, both naturally and anthropogenically, and also used in oral healthcare products and amalgam fillings. We aimed to determine the presence of genes in the oral microbiome conferring reduced susceptibility to common antimicrobials. From an Escherichia coli library, 12,277 clones were screened and ten clones with reduced susceptibility to triclosan were identified. The genes responsible for this phenotype were identified as fabI, originating from a variety of different bacteria. The gene fabI encodes an enoyl-acyl carrier protein reductase (ENR), which is essential for fatty acid synthesis in bacteria. Triclosan binds to ENR, preventing fatty acid synthesis. By introducing the inserts containing fabI, ENR is likely overexpressed in E. coli, reducing the inhibitory effect of triclosan. Another clone was found to have reduced susceptibility to cetyltrimethylammonium bromide and cetylpyridinium chloride. This phenotype was conferred by a UDP-4 glucose-epimerase gene, galE, homologous to one from Veillonella parvula. The product of galE is involved in lipopolysaccharide production. Analysis of the E. coli host cell surface showed that the charge was more positive in the presence of galE, which likely reduces the binding of these positively charged antiseptics to the bacteria. This is the first time galE has been shown to confer resistance against quaternary ammonium compounds and represents a novel, epimerase-based, global cell adaptation, which confers resistance to cationic antimicrobials.

Item Type:	Article
Additional Information:	Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/mdr.2017.0105
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 250 Anti-infective agents (General) QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. QW Microbiology and Immunology > QW 51 Morphology and variability of microorganisms. Microbial genetics.
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1089/mdr.2017.0105
Depositing User:	JISC Pubrouter
Date Deposited:	16 Jun 2017 10:33
Last Modified:	06 Sep 2019 09:34
URI:	https://archive.lstmed.ac.uk/id/eprint/7242

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