2.A.119 The The Organo-Arsenical Exporter (ArsP) Family
In 2014, the first member of the Duf318 family was functionally characterized (Shen et al. 2014). Most are annotated as 'putative permease' or 'permease'. Many members have 8 putative TMSs with two 4 TMS halves separated by a hydrophilic loop of variable sizes. They appear to be restricted to prokaryotes, both bacteria and archaea. Some members are encoded by genes in operons concerned with arsenate/arsenite resistance (Castillo and Saier, 2010). The ArsP protein of Campylobacter jejuni may be distantly related to the VUT family member, TrpP of Bacillus subtilis (2.A.88.4.1) and the ThiW ABC membrane protein homologue, 3.A.1.26.2. These two families (2.A.88 and 3.A.1.26) are known to be homologous but function as secondary versus primary active transporters, respectively.
Campylobacter jejuni, a major foodborne pathogen causing gastroenteritis in humans, is highly prevalent in poultry and is resistant to the organic arsenic compound, roxarsone (4-hydroxy-3-nitrobenzenearsonic acid), which has been used as a feed additive in the poultry industry for growth promotion. Shen et al. (2014) showed that ArsP, a membrane permease containing eight TMSs, contributes to organic arsenic resistance in Campylobacter. Analysis of multiple C. jejuni isolates from various animal species revealed that the presence of an intact arsP gene is associated with elevated resistance to roxarsone. In addition, inactivation of arsP in C. jejuni resulted in a 4-fold reduction in the MICs of roxarsone and nitarsone compared to the wild-type strain. Furthermore, cloning of arsP into a C. jejuni strain lacking a functional arsP led to 8- and 64-fold increases in the MICs of roxarsone and nitarsone, respectively. Neither mutation nor overexpression of arsP affected the MICs of inorganic arsenic including arsenite and arsenate. Moreover, acquisition of the arsP gene in NCTC 11168 accumulated less roxarsone than the wild type strain lacking the arsP gene. These results indicate that ArsP functions as an efflux transporter for extrusion of organic arsenic and contributes to resistance to these compounds in C. jejuni (Shen et al. 2014).
The generalized reaction catalyzed by ArsP is:
Organic arsenic compounds (in) → Organic arsenic compounds (out)