Our laboratory studies N. gonorrhoeae, an obligate human bacterial pathogen that causes the sexually transmitted infection gonorrhea. Gonorrhea has existed within the human population for all of recorded history and remains the second-most commonly reported bacterial sexually transmitted infection in the world today. Gonorrhea continues to be a major public health problem because of rapid acquisition of antibiotic resistance (the CDC identified N. gonorrhoeae as a highest priority superbug threat in 2013), the lack of protective vaccines, the fact that previously infected individuals remain susceptible to re-infection, and the predisposition of infected individuals to acquisition of HIV. Since N. gonorrhoeae has no niche outside of humans, the biology of this organism is exquisitely tailored to life in the human urogenital tract. Not only is N. gonorrhoeae able to exploit the nutritional and environmental conditions at this site, but the bacterium also has an extraordinary ability to thwart challenges by the host immune response. N. gonorrhoeae evades humoral immune recognition by undergoing extensive variation of its surface structures, including high-frequency sequence changes in the N. gonorrhoeae pilin gene that lead to antigenic variation of the type IV pilus. N. gonorrhoeae is also highly adept at surviving confrontations with the innate immune system. Acute gonorrhea is a highly inflammatory disease characterized by the production of an exudate containing large numbers of neutrophils. Although neutrophils are the body's first defenders against bacterial and fungal challenge, neutrophils are ineffective at killing N. gonorrhoeae, and gonorrheal exudates contain viable, infectious bacteria. Our research is currently centered on identifying how N. gonorrhoeae resists neutrophil clearance. We are addressing how neutrophils recognize N. gonorrhoeae, which antimicrobial activities neutrophils direct against N. gonorrhoeae, and how N. gonorrhoeae withstands or thwarts these activities. We use a combination of cell biology, molecular biology, bacterial genetics and biochemistry to address these questions. The insights gleaned from these studies will help us to understand in general how the mucosal innate immune system defends against infection and how pathogens exploit mucosal defenses to aid in colonization and transmission.