Neisseria gonorrhoeae is the etiological agent of the STI, gonorrhea. Resistance to ceftriaxone and azithromycin, the currently recommended treatment for gonococcal infections, is increasing world-wide. Strains resistant to ceftriaxone contain a mosaic penA gene that encodes a highly mutated penicillin-binding protein 2. The mutated PBP2 imparts a fitness deficit, but strains have likely acquired compensatory mutations that alleviate this deficit. The goals of the lab are to identify compensatory mutations that increase the fitness of mosaic penA-containing strains. The lab has characterized an AcnB mutation, G348D, obtained in the mouse model that increases fitness. AcnB is the aconitase enzyme that converts citrate to isocitrate in the TCA cycle, but it also plays a role in post-transcriptional regulation of many other proteins. Our collaborators identified Q371K in clinical isolates that was associated with ceftriaxone resistance. We hypothesized the Q371K mutation found in AcnB will cause an increase in the fitness of resistant gonococcal strains. My project is to characterize the expression of AcnB to determine if it’s similarly regulated and if the mutation alters growth in a manner similar to that caused by the G348D mutation. If AcnB-Q371K increases fitness, this will be the first compensatory mutation identified in human isolates.
