Transcriptomic Responses and Survival Mechanisms of Staphylococci to the Antimicrobial Skin Lipid Sphingosine

Chen, Yiyun, Moran, Josephine C, Campbell-Lee, Stuart and Horsburgh, Malcolm J ORCID: 0000-0002-3806-0039 (2022) Transcriptomic Responses and Survival Mechanisms of Staphylococci to the Antimicrobial Skin Lipid Sphingosine. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 66 (2). e0056921-.

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Abstract

Sphingosines are antimicrobial lipids that form part of the innate barrier to skin colonization by microbes. Sphingosine deficiencies can result in increased epithelial infections by bacteria including Staphylococcus aureus. Recent studies have focused on the potential use of sphingosine resistance or its potential mechanisms. We used RNA-Seq to identify the common d-sphingosine transcriptomic response of the transient skin colonizer S. aureus and the dominant skin coloniser S. epidermidis. A common d-sphingosine stimulon was identified that included downregulation of the SaeSR two-component system (TCS) regulon and upregulation of both the VraSR TCS and CtsR stress regulons. We show that the PstSCAB phosphate transporter, and VraSR offer intrinsic resistance to d-sphingosine. Further, we demonstrate increased sphingosine resistance in these staphylococci evolves readily through mutations in genes encoding the FarE-FarR efflux/regulator proteins. The ease of selecting mutants with resistance to sphingosine may impact upon staphylococcal colonization of skin where the lipid is present and have implications with topical therapeutic applications.

Item Type:	Article
Uncontrolled Keywords:	drug resistance evolution, resistance, skin, Staphylococcus
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	14 Jan 2022 11:03
Last Modified:	18 Jan 2023 21:23
DOI:	10.1128/aac.00569-21
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3144493