Neisseria gonorrhoeae is an obligate human pathogen and causes the sexually-transmitted infection, gonorrhea, which is the second most-common reportable infectious disease in the US. N. gonorrhoeae elicits both localized infections, and very serious sequelae in women, including pelvic inflammatory disease and infertility. While antimicrobial therapy is still effective for treatment of gonorrhea, resistance to antibiotics has emerged and continues to develop. Therefore, strategies to prevent or treat this infectious disease are actively being sought. N. gonorrhoeae expresses a variety of nutrient receptors on its surface, with which the pathogen sequesters iron from its environment. Although mechanisms for utilization of host iron-binding proteins, including transferrin and lactoferrin, have been most thoroughly characterized, expression of these receptors is not required for growth of the gonococcus in all environmental niches. The presence of genes in the gonococcal genome that potentially encode other uncharacterized, high-affinity transporters is consistent with the likelihood that N. gonorrhoeae expresses a diverse complement of iron-specific transporters, which efficiently make available this necessary nutrient. The long-term goal of this research is to identify other functional transporters, to characterize their ligands, to probe their mechanism of uptake, and to determine the biological relevance of interference with receptor function in vivo. These receptors could ultimately be used as vaccine antigens for immunoprophylaxis or could be the target of topical therapeutics to treat gonococcal disease.
The specific aims of this pilot study address the following questions: 1. Are the predicted TonB-dependent transporters required for gonococcal replication inside epithelial cells or for growth with extracellularly-provided iron sources, including xenosiderophores? 2. By what mechanisms do some gonococcal strains bypass the requirement for TonB? This aim is based on the observation that utilization of xenosiderophores and intracellular growth in some strains is largely independent of the characterized TonB locus. ? ? ? ?
