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 σ⁵⁴- and σ²⁸-dependent transcription. In other bacteria, σ28 transcriptional activity is controlled by an anti-σ²⁸ factor, FlgM. We demonstrate that the V. cholerae FlgM homologue (i) physically interacts with σ²⁸, (ii) has a repressive effect on some V. cholerae σ²⁸-dependent flagellar promoters, and (iii) is secreted through the polar sheathed flagellum, consistent with anti-σ²⁸ activity. Interestingly, FlgM does not have a uniform repressive effect on all σ²⁸-dependent promoters, as determined by measurement of σ²⁸-dependent transcription in cells either lacking FlgM (Δflg]M or incapable of secretion (ΔfliF). Further analysis of a ΔfliF strain revealed that this flagellar assembly block causes a decrease in class III (FlrC- and σ⁵⁴-dependent) and class II (FlrA-dependent), but not class II (FlrA- and σ⁵⁴- dependent), flagellar transcription. V. cholerae flgM and fliA (encodes σ²⁸) 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-σ²⁸ factor and that the sheathed flagellum is competent for secretion of nonstructural proteins.