The Vibrio cholerae FlgM homologue is an anti-σ28 factor that is secreted through the sheathed polar flagellum

Vibrio cholerae has a single polar sheathed flagellum that propels the cells of this bacterium. Flagellar synthesis, motility, and chemotaxis have all been linked to virulence in this human pathogen. V. cholerae expresses flagellar genes in a hierarchy consisting of sigma(54)- and sigma(28)-dependent transcription. In other bacteria, sigma(28) transcriptional activity is controlled by an anti-sigma(28) factor, FlgM. We demonstrate that the V. cholerae FlgM homologue (i) physically interacts with sigma(28), (ii) has a repressive effect on some V. cholerae sigma(28)-dependent flagellar promoters, and (iii) is secreted through the polar sheathed flagellum, consistent with anti-sigma(28) activity. Interestingly, FlgM does not have a uniform repressive effect on all sigma(28)-dependent promoters, as determined by measurement of sigma(28)-dependent transcription in cells either lacking FlgM (DeltaflgAl) or incapable of secretion (DeltafliF). Further analysis of a DeltafliF strain revealed that this flagellar assembly block causes a decrease in class III (FlrC- and sigma(54)-dependent) and class IV (sigma(28)-dependent), but not class II (FIrA- and sigma(54)-dependent), flagellar transcription. V. cholerae flgM and fliA (encodes sigma(28)) mutants were only modestly affected in their ability to colonize the infant mouse intestine, a measure of virulence. Our results demonstrate that V. cholerae FlgM functions as an anti-sigma(28) factor and that the sheathed flagellum is competent for secretion of nonstructural proteins.