RfiA, a novel PAP2 domain-containing polytopic membrane protein that confers resistance to the FtsZ inhibitor PC190723

ABSTRACT  Background: As an essential protein for bacterial cell division, the tubulin-like FtsZprotein has been selected as a target for development of next generation antimicrobials. PC190723 is a fluoride-containing benzamidecompound developed as a FtsZinhibitor that selectively inhibits growth of multidrug resistant Gram-positive bacteria. Aim: Our aim was to investigate the mechanism of resistance to PC109723 conferred by over-expression of a gene, rfiA, in an environmental bacterium ArthrobacterA3. Materials & methods: The investigations included analysis of the effect of PC109723 on wild-type ArthrobacterA3 and a recombinant strain over-expressing rfiA, in vivo localization of RfiA, in vitro measurements of fluorine release from PC109723 by membrane extracts from the over-expression strain combined with mass spectrophotometric analysis of reaction products, and modelling of RfiA structure. Results: We describe a novel protein, RfiA, from ArthrobacterA3 that confers PC190723 resistance. RfiA i...