Genomic analysis of Neisseria gonorrhoeae strains from disseminated, urogenital, and rectal infections reveals differences in genes for iron acquisition and type IV secretion

Neisseria gonorrhoeae , an obligate human pathogen, causes the sexually transmitted infection gonorrhea. Delayed treatment or immunodeficiencies can result in a higher risk of disseminated gonococcal infection (DGI), where the infection spreads to normally sterile anatomic sites, including the bloodstream. The gonococcus produces TonB-dependent transporters (TdTs) to sequester metals from host nutritional immunity proteins. These transporters are critical for survival and are important virulence factors. We characterized genes encoding iron-regulated TdTs in the genomes of strains from disseminated ( n = 47), urogenital ( n = 86), and rectal ( n = 12) infections. We found that gonococcal strains isolated from DGI infections were more likely to express a functional hemoglobin-iron utilization operon ( hpuAB wild type and phase on [32%, n = 15/47]), to harbor nonsense mutations in tdfF (57%, n = 27/47), and were predicted to express low levels of fetA (43%, n = 20/47) when compared to strains from urogenital or rectal infections. In contrast, gonococcal strains from localized urogenital infections were associated with a higher frequency of functional tdfF genes (66%, n = 57/86) and high fetA expression (30%, n = 26/86). Additionally, strains from rectal infections were more frequently found to have high fetA expression (33%, n = 4/12) and a functional tdfF (75%, n = 9/12). Furthermore, we identified associations between the presence and absence of tdfF and the gonococcal genetic island, which encodes a type IV secretion system. These findings inform our evolving understanding of the molecular mechanisms underlying disseminated gonococcal infections.