Identification of a Novel Membrane Transporter Mediating Resistance to Organic Arsenic in Campylobacter jejuni
ABSTRACTAlthough bacterial mechanisms involved in the resistance to inorganic arsenic are well understood, the molecular basis for organic arsenic resistance has not been described.Campylobacter jejuni, a major food-borne pathogen causing gastroenteritis in humans, is highly prevalent in poultry and is reportedly resistant to the arsenic compound roxarsone (4-hydroxy-3-nitrobenzenearsonic acid), which has been used as a feed additive in the poultry industry for growth promotion. In this study, we report the identification of a novel membrane transporter (named ArsP) that contributes to organic arsenic resistance inCampylobacter. ArsP is predicted to be a membrane permease containing eight transmembrane helices, distinct from other known arsenic transporters. Analysis of multipleC. jejuniisolates from various animal species revealed that the presence of an intactarsPgene is associated with elevated resistance to roxarsone. In addition, inactivation ofarsPinC. jejuniresulted in 4- and 8-fold reductions in the MICs of roxarsone and nitarsone, respectively, compared to that for the wild-type strain. Furthermore, cloning ofarsPinto aC. jejunistrain lacking a functionalarsPgene led to 16- and 64-fold increases in the MICs of roxarsone and nitarsone, respectively. Neither mutation nor overexpression ofarsPaffected the MICs of inorganic arsenic, including arsenite and arsenate, inCampylobacter. Moreover, acquisition ofarsPin NCTC 11168 led to accumulation of less roxarsone than the wild-type strain lackingarsP. Together, these results indicate that ArsP functions as an efflux transporter specific for extrusion of organic arsenic and contributes to the resistance to these compounds inC. jejuni.