Interplay of virulence factors and signaling molecules: albumin and calcium-mediated biofilm regulation in Bordetella bronchiseptica

Bordetella bronchiseptica, a respiratory pathogen capable of infecting various mammals, including humans, is associated with chronic infections, contrasting with the acute infections caused by Bordetella pertussis. Both pathogens can form biofilm-like structures in vivo, providing tolerance against environmental stresses. Biofilm formation by B. bronchiseptica is regulated by the BvgAS two-component system, with intermediate concentrations of certain modulators inducing a phase favoring biofilm formation. Recent studies have highlighted the role of cyclic diguanylate monophosphate (c-di-GMP) in this process: elevated c-di-GMP levels stimulate biofilm formation, whereas phosphodiesterase (PDE) activation reduces biofilms. Respiratory secretions, which contain albumin and calcium at higher concentrations than standard growth media, promote an increase in the amount and extracellular localization of the adenylate cyclase toxin (ACT), an important Bordetella spp. virulence factor. Secreted ACT present in the extracellular media or attached to the outer membrane inhibits biofilm formation. Based on these observations, we hypothesized that serum albumin and calcium together inhibit biofilm formation and explored the potential role of c-di-GMP in this process. Our findings demonstrate that serum albumin and calcium inhibit B. bronchiseptica biofilm formation by two apparently independent mechanisms, increasing AC secretion and inducing c-di-GMP degradation. This study contributes to the understanding of the mechanisms governing B. bronchiseptica biofilm formation and its modulation by host factors.