Carbon storage regulator A (CsrA Bb) is a repressor of Borrelia burgdorferi flagellin protein FlaB

Abstract

The Lyme disease spirochete Borrelia burgdorferi lacks the transcriptional cascade control of flagellar protein synthesis common to other bacteria. Instead, it relies on a post-transcriptional mechanism to control its flagellar synthesis. The underlying mechanism of this control remains elusive. A recent study reported that the increased level of BB0184 (CsrA Bb; a homologue of carbon storage regulator A) substantially inhibited the accumulation of FlaB, the major flagellin protein of B.burgdorferi. In this report, we deciphered the regulatory role of CsrA Bb on FlaB synthesis and the mechanism involved by analysing two mutants, csrA Bb- (a deletion mutant of csrA Bb) and csrA Bb+ (a mutant conditionally overexpressing csrA Bb). We found that FlaB accumulation was significantly inhibited in csrA Bb+ but was substantially increased in csrA Bb-. In contrast, the levels of other flagellar proteins remained unchanged. Cryo-electron tomography and immuno-fluorescence microscopic analyses revealed that the altered synthesis of CsrA Bb in these two mutants specifically affected flagellar filament length. The leader sequence of flaB transcript contains two conserved CsrA-binding sites, with one of these sites overlapping the Shine-Dalgarno sequence. We found that CsrA Bb bound to the flaB transcripts via these two binding sites, and this binding inhibited the synthesis of FlaB at the translational level. Taken together, our results indicate that CsrA Bb specifically regulates the periplasmic flagellar synthesis by inhibiting translation initiation of the flaB transcript. © 2011 Blackwell Publishing Ltd.