The effect of skin fatty acids on Emphasis Type="

Authors: Yvonne Neumann Knut Ohlsen Stefanie Donat Susanne Engelmann Harald Kusch Dirk Albrecht Michael Cartron Alexander Hurd Simon J Foster

Publish Date: 2014/10/18

Volume: 197, Issue: 2, Pages: 245-267

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Abstract

Staphylococcus aureus is a commensal of the human nose and skin Human skin fatty acids in particular cis6hexadecenoic acid C6H have high antistaphylococcal activity and can inhibit virulence determinant production Here we show that subMIC levels of C6H result in induction of increased resistance The mechanisms of C6H activity was investigated by combined transcriptome and proteome analyses Proteome analysis demonstrated a pleiotropic effect of C6H on virulence determinant production In response to C6H transcriptomics revealed altered expression of over 500 genes involved in many aspects of virulence and cellular physiology The expression of toxins hla hlb hlgBC was reduced whereas that of host defence evasion components cap sspAB katA was increased In particular members of the SaeRS regulon had highly reduced expression and the use of specific mutants revealed that the effect on toxin production is likely mediated via SaeRSThe Grampositive bacterium Staphylococcus aureus is able to survive as a commensal organism in the anterior nares and on human skin A third of the human population are nasal carriers and twothirds are intermittent carriers forming a large reservoir for potential infection Peacock et al 2001 As a pathogen S aureus is highly adaptable with an alarming spread of antibiotic resistance This limits the range of effective therapies able to combat this organism S aureus is able to cause a wide range of diseases from minor skin infections to severe systemic disease such as bacteraemia septic arthritis and endocarditis Also in the hospital environment S aureus is responsible for many infections associated with surgical wounds and catheters The ability to inhabit so many niches with such a range of infectious sequelae is due to a large repertoire of virulence determinantsThe human body has many innate defence mechanisms to prevent infection by invading microbes Physical barriers human skin and mucosa prevent pathogens from ingress The human skin is composed of tightly bound epithelial cells and covered by a highly crosslinked layer of keratin and is therefore normally impenetrable to bacteria Proksch et al 2008 Additionally the skin produces antimicrobial peptides as well as skin fatty acids which are crucial for host defence Ong et al 2002 Niyousaba and Ogawa 2005 Several fatty acids have been isolated from human skin which have strong antimicrobial activity Miller et al 1988 Wille and Kydonieus 2003 The antibacterial activity of unsaturated fatty acids has been well known for many years Kabara et al 1972 Knapp and Melly 1986 Shin et al 2007 the most effective antistaphylococcal skin fatty acid being cis6hexadecanoic acid C6H sapienic acid C161Δ6 Takigawa et al 2005 Wille and Kydonieus 2003 As well as being antibacterial C6H also has the ability to inhibit virulence determinant production and the induction of antibiotic resistance mechanisms Clarke et al 2007 Projan et al 1994 Schlievert et al 1992 Takigawa et al 2005 Kenny et al 2009 In fact in murine models of S aureus infection C6H has shown to be an effective treatment Thus it is important to understand how C6H mediates its effects and the response of S aureus to such assault A surface protein IsdA has been shown to be involved in resistance of S aureus to C6H by rendering the cells more hydrophilic Clarke et al 2007 Also wall teichoic acids are required to prevent susceptibility to C6H Kohler et al 2009

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