Neisseria gonorrhoeae and Neisseria meningitidis affect more than 100 million people worldwide every year, despite the existence of treatment and prevention methods. The emergence of antimicrobial resistance will curtail our ability to effectively manage these infections, making it critical to expand our knowledge of Neisseria biology. Commensal Neisseria provide a tool by which we can dissect one common but poorly understood facet of pathogenic Neisseria behavior, asymptomatic infection. N. gonorrhoeae and N. meningitidis descended from a commensal ancestor and share many host interaction factors with human adapted commensal Neisseria. The central hypothesis of this application proposes that the mechanistic roots of Neisseria asymptomatic infection are commensal in origin, and that the study of conserved host interaction factors provides insight into commensal colonization and asymptomatic infection alike. To test this, I utilize a mouse-Neisseria model of asymptomatic carriage to systematically evaluate a subset of conserved host interaction factors, guided by preliminary data obtained from a transposon mutagenesis and screening approach. In Aim 1, I examine the impact of Type IV pilus retraction during host modulation and inter-bacterial signaling. In Aim 2, I evaluate the contribution of previously uncharacterized polysaccharide biosynthesis genes on structure and function of commensal capsule. In Aim 3, I test the activity and repertoire of a putative Neisseria Type XI secretion system homolog to identify novel surface expressed host interaction factors. My career development strategy supports my research goals through a rigorous schedule of workshops and trainings on grant writing, laboratory management, and mentorship. These activities are designed to help me successfully transition to independence, making me uniquely positioned to improve our understanding of Neisseria-host interaction

Infections caused by pathogenic Neisseria impose a significant burden on public health. Asymptomatic infections, a common outcome of Neisseria-host interaction, contribute to disease but are poorly understood; these infections may have roots in commensal Neisseria niche development and maintenance behaviors. This project will dissect the mechanisms driving pathogenic Neisseria asymptomatic carriage through the study of host interaction factors shared between commensal and pathogenic Neisseria using an in vivo model of long-term asymptomatic carriage.