We study the molecular mechanisms by which bacteria exploit host-derived nutrients to thrive at sites of inflammation. Our laboratory uses bacterial genetics, molecular biology, omics, computational systems biology to investigate metabolic cross-talk between Neisseria gonorrhoeae (the gonnococcus, Gc) and the innate immune system. Gc is the causative agent of the STI gonnorhea. There is no protective vaccine against this organism and "superbug" strains resistant to all clinically recommended antibiotics have been found globally. This bacteria induces severe life-long clinical sequelae, particularly in women, including pelvic inflammatory disease, ectopic pregnancy, and sterility. These sequelae are caused in part, by unresolved inflammation initiated by prolific neutrophil influx to the infection site. Neutrophils use potent cytotoxic compounds to kill bacteria, and are the primary innate immune responders to Gc infection. Yet Gc are one of the few bacteria capable of surviving in the presence of neutrophils. This is enabled in part, by exploitation of neutrophils as sources of nutrition by Gc during infection. By understanding this metabolic interplay, we can develop better therapies to prevent and treat these antimicrobial resistant infections.

We have three projects available in the lab:

1. Define how inflammation in the genital tract dictates Gc central metabolism. Gc is a fascinating pathogen because it is exquisitely adapted to the human host and has limited metabolic capabilities compared to other bacterial pathogens. Sites of neutrophilic inflammation are hypoxic, replete for innate immune radicals, and nutrient limited. Yet Gc can thrive in the presence of neutrophils. We seek to understand how these metabolic stressors shape Gc metabolism in its obligate human host.

2. Determine the effect of the inflamed genital tract environment on neutrophil antibacterial immunity towards Gc. Lactate, which is an abundant metabolite within the female genital tract, is also a potent signaling molecule. We are investigating how this key metabolite shapes neutrophil immunometabolism in response to Gc infection.

3. Identify and target metabolic pathways that enhance Gc antimicrobial resistance. There is one remaining antibiotic clinically recommended for treatment of Gc. Given the significance of Gc as a widespread, highly antibiotic resistant bacteria, we are interested in metabolic drivers of Gc antimicrobial resistance, that can be targeted as an Achilles’ heel to prevent antimicrobial resistant infections.