Bordetella bronchiseptica diguanylate cyclase BdcB inhibits the type three secretion system and impacts the immune response

Bordetella bronchiseptica is a gram-negative bacterium that causes respiratory diseases in different animals, including mice, making B. bronchiseptica the gold-standard model to investigate host-pathogen interaction at the molecular level. B. bronchiseptica utilizes many different mechanisms to precisely regulate the expression of virulence factors. Cyclic di-GMP is a second messenger synthesized by diguanylate cyclases and degraded by phosphodiesterases that regulates the expression of multiple virulence factors including biofilm formation. As in other bacteria, we have previously shown that c-di-GMP regulates motility and biofilm formation in B. bronchiseptica. This work describes the diguanylate cyclase BdcB (Bordetelladiguanylate cyclase B) as an active diguanylate cyclase that promotes biofilm formation and inhibits motility in B. bronchiseptica. The absence of BdcB increased macrophage cytotoxicity in vitro and induced a greater production of TNF-alpha, IL-6, and IL-10 by macrophages. Our study reveals that BdcB regulates the expression of components of T3SS, an important virulence factor of B. bronchiseptica. The Bb increment bdcB mutant presented increased expression of T3SS-mediated toxins such as bteA, responsible for cytotoxicity. Our in vivo results revealed that albeit the absence of bdcB did not affect the ability of B. bronchiseptica to infect and colonize the respiratory tract of mice, mice infected with Bb increment bdcB presented a significantly higher pro-inflammatory response than those infected with wild type B. bronchiseptica.

Automated summary

Bordetella bronchiseptica is a gram-negative bacterium that serves as a model for studying host-pathogen interactions. This study identifies the diguanylate cyclase BdcB as an important regulator of biofilm formation and motility in B. bronchiseptica. The absence of BdcB leads to increased cytotoxicity and pro-inflammatory response in macrophages, as well as upregulation of T3SS-mediated toxins. These findings highlight the role of BdcB in virulence regulation and host immune response in B. bronchiseptica.