Pertussis 'Signal Switch': c-di-GMP Regulatory Network May Become a New Anti-infective Target
Recently, a systematic review published in FEMS Microbiology Reviews comprehensively analyzed, for the first time, the molecular architecture and regulatory functions of the c‑di‑GMP second‑messenger signaling network in classical Bordetella species (including B. pertussis, B. bronchiseptica, and others), offering a new perspective on the pathogenesis of respiratory pathogens such as pertussis.
c‑di‑GMP is a ubiquitous bacterial second messenger that regulates key processes including biofilm formation, motility, and virulence. The review notes that in B. bronchiseptica, elevated c‑di‑GMP levels significantly promote biofilm development while suppressing type III secretion system expression, thereby reducing bacterial cytotoxicity toward host cells. Animal experiments showed that strains with abnormally high c‑di‑GMP levels exhibited markedly reduced colonization in the mouse respiratory tract and elicited a weaker immune response.
Of particular note, the research team proposed a non‑canonical model for the BvgR protein—although it lacks phosphodiesterase catalytic activity, it may act as a non‑catalytic c‑di‑GMP effector that regulates virulence gene expression through protein‑protein interactions. This finding challenges conventional understanding and provides a theoretical basis for developing novel anti‑infective drugs targeting the c‑di‑GMP signaling pathway.
Furthermore, the study revealed that B. pertussis, due to genome reduction during evolution, retains only nine c‑di‑GMP‑metabolizing enzymes, far fewer than the 21 found in B. bronchiseptica. This streamlined network architecture may serve as a breakthrough for selective drug intervention. The review concludes that elucidating the sensory ligands and effector mechanisms of this signaling network will offer new strategies to address the global public health challenge of pertussis resurgence.
FOR DETAIL: https://doi.org/10.1093/femsre/fuaf065
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