The virulence regulator bvgS is required for nutrient-induced filamentation in Bordetella avium

Bacteria can change morphology in response to stressors and changes in their environment, including infection of a host. We previously identified the bacterial species, Bordetella atropi, which uses nutrient-induced filamentation as a novel mechanism for cell-to-cell spreading in the intestinal epithelial cells of a nematode host. To further investigate the conservation of nutrient-induced filamentation in Bordetellae, we utilized the turkey-infecting species Bordetella avium which filaments in vitro when switched from a standard growth media to an enriched media. We conducted a selection-based filamentation screen with B. avium and isolated two independent non-filamentous mutants that failed to filament in highly enriched media. These mutants contained different alleles in bvgS, the sensor in the two-component master virulence regulator (BvgAS) conserved across the Bordetella genus. To investigate the role of bvgS in nutrient-induced filamentation, we conducted transcriptomics and found that bvgS mutation resulted in loss of responsiveness to highly-enriched media, especially in genes related to nutrient uptake and metabolism. The most dysregulated gene in the bvgS mutant encoded for succinyl-CoA:acetate CoA-transferase (SCACT) and we were able to regulate filamentation with exogenous metabolites up and downstream of this enzyme. These data suggest that bvgS regulates nutrient-induced filamentation by controlling metabolic capacity. Overall, we found that the virulence regulator bvgS is required for nutrient-induced filamentation in B. avium, suggesting there may be conservation in Bordetellae for utilizing this morphological change as a virulence phenotype.