The genus Neisseria contains many species. Most of them are part of the normal flora of humans and animals; only two are human pathogens: Neisseria gonorrhoeae, which causes a sexually transmitted disease of the same name, and Neisseria meningitidis, which causes meningitis. These pathogens often behave like their related commensal cousins in that they establish asymptomatic infection at high frequency. This commensal-like trait was likely inherited by the pathogens as they evolved from commensal species. Supporting this idea is the observation that many N. gonorrhoeae and N. meningiditis genes that mediate pathogen interactions with their hosts are also in the commensals. A major goal of our lab is to determine how commensal and pathogenic Neisseria differentially regulate these host interaction genes, and how these regulatory events might affect their lifecycle in the host.
Another goal of our lab is to use our new mouse model for Neisseria colonization, persistence, and asymptomatic infection to determine the mechanistic bases of these events. Due to the strict tropism of human-dwelling Neisseria for man, there is a dearth of animal models for studying Neisseria-host interactions; most of these studies require cultured human cells. Together with immunologist Jeff Frelinger in our department, we have developed a mouse model which, for the first time, allows us to study Neisseria colonization, persistence, and asymptomatic infection from standpoint of both the bacterium and the host. This system will also be useful for developing antibiotics and testing vaccine efficacy against the pathogens.
Our lab also wishes to understand how Neisseria species signal the epithelia so as to survive the antibacterial mechanisms mounted by the host. The bacteria tug on the epithelial cell membrane by means of the PilT motor complex in their Type IV pili. The physical force created by tugging transduces mechanical signals to the infected cell, reprograming its cell transcriptional activity, redirecting its protein trafficking, and inducing anti-apoptotic signaling pathways that ultimately preserve the integrity of the infected cell. Our goal is to understand how the PilT motor induces these epithelial cell responses, and to use our animal model to examine the in vivo functions of the Type IV pilus.