Genotypic virulence profiles and mobile genetic elements related to invasiveness in Neisseria gonorrhoeae strains

Neisseria gonorrhoeae (NG) has become an increasing global health threat due to drug resistance and potentially invasive disease. In this study, we assessed the genotypic profile in both invasive and non-invasive NG strains from patients at University of Sao Paulo Faculty of Medicine Clinics Hospital, Brazil. We analyzed the NG genotypic profiles and clinical data from 25 patients hospitalized at Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP) from January 2017 to March 2020. A total of 25 isolates underwent whole genome sequencing, of which 10 (40%) were collected from sterile sites like blood and classified as invasive. Invasive and noninvasive specimens were clustered in 5 STs and 11 STs, respectively, sharing 3 STs in common. We identified resistance markers for macrolides (mtrR) in 40% of isolates and 92% exhibited at least one resistance marker for beta-lactams (penA, blaTEM-1B, or blaTEM-135), predominantly PBP1 and PBP2 alterations. Resistance genes blaTEM-1B (7%vs.50%, p=0.023) and tetM (13%vs.80%, p=0.002) were more frequently found in invasive disease isolates, always accompanied by the mobile genetic elements pJD4 and pEP5289, respectively. Associated with these elements were two toxin encoding genes (vapD and zeta1/2) previously described as possible virulence factors and resistance genes for beta-lactams and tetracyclines. Results revealed that invasive strains of NG are genotypically clustered and frequently harbor two plasmids which may be associated with invasive disease. Resistance markers for beta-lactam as PBP1 and PBP2 alterations warn against a future potential resistance to this class.