title: Staphylococcus aureus MnhF mediates cholate efflux and facilitates survival under human colonic conditions.
abstract: Resistance to the innate defenses of the intestine is crucial for the survival and carriage of Staphylococcus aureus, a common colonizer of the human gut. Bile salts produced by the liver and secreted into the intestines are one such group of molecules with potent antimicrobial activity. The mechanisms by which S. aureus is able to resist such defenses in order to colonize and survive in the human gut are unknown. Here we show that mnhF confers resistance to bile salts, which can be abrogated by efflux pump inhibitors. MnhF mediates the efflux of radiolabeled cholic acid both in S. aureus and when heterologously expressed in Escherichia coli, rendering them resistant. Deletion of mnhF attenuated the survival of S. aureus in an anaerobic three-stage continuous-culture model of the human colon (gut model), which represents different anatomical areas of the large intestine.
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights, Reading, United Kingdom.
authors.forename: Thippeswamy H
authors.initials: TH
authors.lastname: Sannasiddappa
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights, Reading, United Kingdom.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hood
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights, Reading, United Kingdom.
authors.forename: Kevan J
authors.initials: KJ
authors.lastname: Hanson
authors.affiliation: Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom.
authors.forename: Adele
authors.initials: A
authors.lastname: Costabile
authors.affiliation: Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom.
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gibson
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights, Reading, United Kingdom s.r.clarke@reading.ac.uk.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Clarke
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020355:Cholates / Q000378:metabolism*; D003001:Cloning, Molecular; D003106:Colon / Q000382:microbiology / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020355:Cholates
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