Phenotypic diversity and shared genomic determinants among isolates causing a large incidence of disseminated...

The incidence of disseminated gonococcal infection (DGI) has remained low since the advent of antibiotics; however, a recent surge in DGI has inexplicably emerged during the past decade. In an effort to understand whether Neisseria gonorrhoeae that cause disseminated disease can be differentiated from non-invasive strains, we have performed a phenotypic and genotypic analysis on a selection of isolates obtained from invasive and uncomplicated infections in Canada. The increase in DGI was initially associated with a single antibiotic-susceptible gonococcal lineage, but later cases have been caused by diverse strains. Phenotypic analysis of a matched subset of 20 isolates obtained since 2013 found that these varied in their capacity to aggregate in suspension and in their association with serum complement proteins; however, these interactions did not discriminate between the invasive and mucosal isolates. Sequence typing of 360 Canadian isolates revealed that two variant porBa alleles are significantly associated with the DGI strains, one of these being present throughout the past decade, whereas the other emerged more recently. A PopNet-based population dynamics analysis, which instead establishes relationships based upon variance among discrete chromosomal segments, revealed that DGI isolates were restricted to distinct subpopulations within their phylogenetic distribution, implying a genetically linked potential to cause invasive disease. Consistent with this, a large number of genetic determinants are enriched in the DGI strains, making these enticing candidates to explain the increased capacity of N. gonorrhoeae to cause systemic infection and/or reduce the presentation of clinical symptoms from localized infection so that it remains untreated.IMPORTANCEThe re-emergence of disseminated gonococcal infections (DGIs) has raised concern that the virulence of some strains has increased due to their acquisition of a new capacity to remain asymptomatic during uncomplicated mucosal infection and/or to invade the bloodstream and persist upon establishing colonization at distal tissue sites. The molecular epidemiology of a very large incidence of DGI in Canada, which began from a single strain but then diversified with time, provided an opportunity to understand whether the invasive isolates were either phenotypically or genotypically related. While classical phenotypic analysis did not discriminate between mucosal and invasive isolates, a population dynamics-based approach established that the DGI isolates are present within distinct subpopulations of Neisseria gonorrhoeae and reveals genetic determinants that are linked to this phenotype. This suggests that the DGI phenotype emerged multiple times independently and/or the genetic features responsible have been transmitted among the populations.