Genomic analysis of urogenital and rectalNeisseria meningitidisisolates reveals encapsulated hyperinvasive meningococci and coincident multidrug-resistant gonococci

Abstract

ObjectiveInvasive 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.MethodsMeningococci 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.ResultsAs 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.ConclusionsThese 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.

Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operon

“…The US_NmUC has emerged as urogenital pathogen. Historically, Nm is not recognized as a significant cause of urogenital infection and the occasional meningococci recovered from such isolated cases have been from diverse serogroups and lineages (Harrison et al, 2017;Ma et al, 2017). The recent urethritis outbreaks and clusters caused by US_NmUC suggest that with novel genetic and phenotypic changes, this meningococcal clade is being transmitted efficiently between sexual partners and can successfully resist local innate immune responses (Bazan et al, 2016;Toh et al, 2017;Tzeng et al, 2017;Retchless et al, 2018).…”

Development of a SimpleProbe real-Time PCR Assay for rapid detection and identification of the US novel urethrotropic clade of Neisseria meningitidis ST-11 (US_NmUC)

“…Both SNPs were present in all of the US_NmUC isolates. We also evaluated if 184 invasive NM strains, 9 urethritis/proctitis-associated NM strains from Europe [21,22,36], and 913 NG strains available in PubMLST encoded norB alleles and, if so, contained the US_NmUC associated SNPs [27]. We identified norB alleles in 41 of the invasive NM strains, 7 of the European urethritis/ proctitis-associated NM strains, and in all of the NG strains.…”

“…Neisseria meningitidis (NM) is best known for its ability to invade and cause meningitis and septicemia, although these invasive infections are rare and asymptomatic nasopharyngeal NM colonization is more common [13,14]. NM has previously been associated with single cases and small clusters of urethritis cases [15][16][17][18][19][20][21][22], but none of these earlier outbreaks were sustained.…”

Atypical, Yet Not Infrequent, Infections with Neisseria Species

“…A recent analysis of urogenital and rectal infections revealed co-colonization with encapsulated, hyperinvasive meningococci and closely related MultiDrug-Resistant (MDR) gonococci [88]. The main concern with co-infection is an increased chance that meningococci acquire gonococcal antimicrobial resistance genes.…”