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

BELHART, KEILA; SISTI, FEDERICO; CARTELLE GESTAL, MÓNICA*; FERNANDEZ, JULIETA*

Scientific Reports (Sci Rep)

Springer Nature

Año: 2023

Bordetella bronchiseptica is a gram-negative bacterium that causes respiratory diseases in differentanimals, including mice, making B. bronchiseptica the gold-standard model to investigate host–pathogen interaction at the molecular level. B. bronchiseptica utilizes many different mechanisms toprecisely regulate the expression of virulence factors. Cyclic di-GMP is a second messenger synthesizedby diguanylate cyclases and degraded by phosphodiesterases that regulates the expression ofmultiple virulence factors including biofilm formation. As in other bacteria, we have previously shownthat c-di-GMP regulates motility and biofilm formation in B. bronchiseptica. This work describes thediguanylate cyclase BdcB (Bordetella diguanylate cyclase B) as an active diguanylate cyclase thatpromotes biofilm formation and inhibits motility in B. bronchiseptica. The absence of BdcB increasedmacrophage cytotoxicity in vitro and induced a greater production of TNF-α, IL-6, and IL-10 bymacrophages. Our study reveals that BdcB regulates the expression of components of T3SS, animportant virulence factor of B. bronchiseptica. The BbΔbdcB mutant presented increased expressionof T3SS-mediated toxins such as bteA, responsible for cytotoxicity. Our in vivo results revealedthat albeit the absence of bdcB did not affect the ability of B. bronchiseptica to infect and colonizethe respiratory tract of mice, mice infected with BbΔbdcB presented a significantly higher proinflammatoryresponse than those infected with wild type B. bronchiseptica.