Neisseria gonorrhoeae is a highly contagious sexually transmitted disease that causes gonorrhea. Gonorrhea is associated with inflammation of the urethra or cervix, and is capable of causing permanent health problems when left untreated. Although there are antibiotics to treat N. gonorrhoeae, they are less effective as the pathogenic bacteria has become increasingly drug-resistant. Two N. gonorrhoeae mutants were used to better understand the role of specific genes in bacterial interaction with the human innate immune system. The innate immune system is critical for protecting hosts against bacterial infections, including those by N. gonorrhoeae. The first N. gonorrhoeae mutant has a mutation in the internal response regulator gene (MisR gene), which is part of a two-component regulatory system. Two-complement regulatory systems are commonly used by bacteria to sense environmental changes and respond to these changes. The exterior sensor kinase sends signals to the response regulator gene inside of the bacterial cell which then causes changes in transcription and gene expression. Mutations within the MisR gene of Neisseria meningitidis have been shown to be important for bacterial survival against components of the innate immune system and caused a weakened meningococcal infection in mice. The second N. gonorrhoeae mutant has a mutation is in the acetate kinase (AckA) gene. This mutant has been shown to have an increased protein acetylation phenotype. Our experiments will determine how these mutations impact bacterial survival during bacterial interaction with human serum and human innate immune cells such as neutrophils, monocytes, and macrophages. We will carry out bactericidal assays as well as neutrophil, monocyte, and macrophage killing assays with wild-type N. gonorrhoeae and each mutant strain of N. gonorrhoeae. The data collected will give new information concerning the role of the role of the MisR and AckA genes in N. gonorrhoeae survival against the human innate immune system.