Virulence-associated gene 8 protein (Vag8) (Vag8)

Virulence-associated gene 8 protein (Vag8) is a 95-kDa autotransporter protein secreted by Bordetella pertussis, the primary pathogen responsible for whooping cough [1, 3, 8]. It serves as a critical virulence factor by mediating the bacterium's resistance to the host's innate immune system, specifically through the inactivation of the human C1 esterase inhibitor (C1-INH) [1, 5]. By binding to the reactive center loop of C1-INH, Vag8 prevents this regulator from inhibiting proteases in the complement and contact systems, which leads to uncontrolled complement consumption and the generation of bradykinin [2, 6]. The resulting increase in bradykinin levels is hypothesized to be a major contributor to the paroxysmal cough that characterizes pertussis infections [2, 4, 6]. Due to its surface-exposed nature and its role in pathogenesis, Vag8 is a prominent candidate for inclusion in next-generation acellular pertussis vaccines to enhance protective immunity [2, 9]. While no small-molecule drugs currently target Vag8, experimental studies have shown that neutralizing antibodies against the protein can effectively reduce bacterial colonization and protect against infection in animal models [2, 12].

Other names

Virulence-activated gene 8 protein95-kDa autotransporter proteinC1 inhibitor-binding protein

Vag8 binds to and inactivates human C1 esterase inhibitor (C1-INH) by sequestering its reactive center loop, which prevents C1-INH from regulating the complement and contact systems, thereby promoting bacterial survival and bradykinin-mediated inflammation.