ABSTRACT
The
farAB operon of Neisseria gonorrhoeae encodes an
efflux pump which mediates gonococcal resistance to antibacterial fatty
acids. It was previously observed that expression of the farAB
operon was positively regulated by MtrR, which is a repressor of the
mtrCDE-encoded efflux pump system (E.-H. Lee and W.
M. Shafer, Mol. Microbiol. 33:839-845, 1999). This regulation
was believed to be indirect since MtrR did not bind to the
farAB promoter. In this study, computer analysis of the
gonococcal genome sequence database, lacZ reporter fusions,
and gel mobility shift assays were used to elucidate the regulatory
mechanism by which expression of the farAB operon is modulated
by MtrR in gonococci. We identified a regulatory protein belonging to
the MarR family of transcriptional repressors and found that it
negatively controls expression of farAB by directly binding to
the farAB promoter. We designated this regulator FarR to
signify its role in regulating the farAB operon. We found that
MtrR binds to the farR promoter, thereby repressing
farR expression. Hence, MtrR regulates farAB in a
positive fashion by modulating farR expression. This MtrR
regulatory cascade seems to play an important role in adjusting levels
of the FarAB and MtrCDE efflux pumps to prevent their excess expression
in
gonococci.
Insights into Protein Allostery in the CsoR/RcnR Family of Transcriptional Repressors