The virulence regulator <i>bvgS</i> controls nutrient-induced filamentation in <i>Bordetella avium</i>

Bacteria can change morphology in response to stressors and changes in their environment, including infection of a host. We previously identified the bacterial species, <i>Bordetella atropi</i>, 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 <i>Bordetella avium,</i> which filaments <i>in vitro</i> when switched from a standard growth media to an enriched media. We conducted a selection-based filamentation screen with <i>B. avium</i> and isolated two independent non-filamentous mutants that failed to filament in highly enriched media. These mutants contained different alleles in <i>bvgS,</i> the sensor in the two-component master virulence regulator (BvgAS) conserved across the <i>Bordetella</i> genus. To investigate the role of <i>bvgS</i> in nutrient-induced filamentation, we conducted transcriptomics and found that our allele of <i>bvgS</i> resulted in loss of responsiveness to highly enriched media, especially in genes related to nutrient uptake and metabolism. The most dysregulated gene in the <i>bvgS</i> mutant encoded for succinyl-CoA:acetate CoA-transferase, and we were able to regulate filamentation with exogenous metabolites up and downstream of this enzyme. These data suggest that <i>bvgS</i> regulates nutrient-induced filamentation by controlling metabolic capacity. Overall, we found that the virulence regulator <i>bvgS</i> can control nutrient-induced filamentation in <i>B. avium,</i> suggesting there may be conservation in Bordetellae for utilizing this morphological change as a virulence phenotype.IMPORTANCE<i>Bordetella avium</i> is the causative agent of bordetellosis, an infectious disease affecting the respiratory system of birds, significantly increasing morbidity in poultry, ultimately leading to economic losses. It is long known that the pathogenesis of <i>B. avium</i> is governed by the two-component master virulence regulator, BvgAS. However, this regulon has never before been associated with nutrient-induced filamentation. In this study, we identify BvgS to be regulating nutrient-induced filamentation. We also report the first transcriptomics analysis of filamentous <i>B. avium</i>, showing the enzyme succinyl-CoA:acetate CoA-transferase may be involved in a metabolic shift in enriched nutrient conditions leading to filamentation. Our results suggest that virulence in <i>B. avium</i> is a dynamic relationship, affected by nutrient availability, rather than a simple binary decision.