Genomic analysis of urogenital and rectal Neisseria meningitidis isolates reveals encapsulated hyperinvasive meningococci and coincident multidrug-resistant gonococci

Abstract

Objective: Invasive meningococcal disease (IMD) outbreaks in men who have sex with men (MSM) have been associated with meningococcal colonisation of the urethra and rectum, but little is known about this colonisation or co-colonisation with the closely related gonococcus. Whole genome sequencing (WGS) was employed to explore these phenomena.

Methods: Meningococci isolated from the urogenital tract and rectum (n=23) and coincident gonococci (n=14) were analysed by WGS along with contemporary meningococci from IMD (n=11). All isolates were obtained from hospital admissions in Brighton, UK, 2011-2013. Assembled WGS were deposited in the PubMLST/neisseria database (http://pubmlst.org/neisseria) and compared at genomic loci common to gonococci or meningococci.

Results: As expected, most meningococci from IMD were encapsulated and belonged to hyperinvasive lineages. So too were meningococci found in the urogenital tract and rectum, contrasting to those asymptomatically carried in the nasopharynx where such meningococci are rare. Five hyperinvasive meningococcal lineages and four distinct gonococcal genotypes were recovered, including multiresistant ST-1901 (NG MAST-1407) gonococci.

Conclusions: These data were consistent with a predisposition for potentially virulent encapsulated hyperinvasive meningococci to colonise the urethra and rectum, which suggests their involvement in MSM IMD outbreaks. The coincidence of multiresistant gonococci raises wider public health concerns.

Keywords: INFECTIOUS DISEASES; MENINGITIS; NEISSERIA GONORRHOEA; NEISSERIA MENINGITIS.

Figure 1

Neisseria meningitidis genome comparison. NeighborNet tree depicting N. meningitidis isolates compared using 1605 loci core to the meningococcal genome (N. meningitidis cgMLST V.1.0). Stars depict invasive meningococcal disease cases; black squares N. meningitidis isolates obtained from urethral samples; black circles N. meningitidis isolates retrieved from rectal swabs. A1, B2, D4 and so on indicate concomitant N. gonorrhoeae infections. (B) serogroup B, (C) serogroup C, (E) serogroup E, (Y) serogroup Y, (Z) serogroup Z, (cnl) capsule null. IMD, invasive meningococcal disease

Figure 2

Neisseria gonorrhoeae genome comparison. NeighborNet tree depicting N. gonorrhoeae isolates compared using the 1668 loci core to the gonococcal genome (N. gonorrhoeae cgMLST V.1.0). Black squares depict isolates obtained from urethral samples; black circles isolates retrieved from rectal swabs with triangles indicating nasopharyngeal isolates. Red circles depict gonococci resistant to multiple antimicrobial compounds including third-generation cephalosporins and fluoroquinolones; pink circles indicate gonococci resistant to fluoroquinolones and penicillin, while green circles depict antimicrobial susceptible gonococci.