Emergence of a new Neisseria meningitidis clonal complex 11 lineage 11.2 clade as an effective urogenital pathogen

Abstract

Neisseria meningitidis (Nm) clonal complex 11 (cc11) lineage is a hypervirulent pathogen responsible for outbreaks of invasive meningococcal disease, including among men who have sex with men, and is increasingly associated with urogenital infections. Recently, clusters of Nm urethritis have emerged primarily among heterosexual males in the United States. We determined that nonencapsulated meningococcal isolates from an ongoing Nm urethritis outbreak among epidemiologically unrelated men in Columbus, Ohio, are linked to increased Nm urethritis cases in multiple US cities, including Atlanta and Indianapolis, and that they form a unique clade (the US Nm urethritis clade, US_NmUC). The isolates belonged to the cc11 lineage 11.2/ET-15 with fine type of PorA P1.5–1, 10–8; FetA F3-6; PorB 2–2 and express a unique FHbp allele. A common molecular fingerprint of US_NmUC isolates was an IS1301 element in the intergenic region separating the capsule ctr-css operons and adjacent deletion of cssA/B/C and a part of csc, encoding the serogroup C capsule polymerase. This resulted in the loss of encapsulation and intrinsic lipooligosaccharide sialylation that may promote adherence to mucosal surfaces. Furthermore, we detected an IS1301-mediated inversion of an ∼20-kb sequence near the cps locus. Surprisingly, these isolates had acquired by gene conversion the complete gonococcal denitrification norB-aniA gene cassette, and strains grow well anaerobically. The cc11 US_NmUC isolates causing urethritis clusters in the United States may have adapted to a urogenital environment by loss of capsule and gene conversion of the Neisseria gonorrheae norB-aniA cassette promoting anaerobic growth.

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

“…The standard pigeonholing of these species—while a convenient shorthand—belies the clinical observations that not all the Gram negative diplococci that cause “gonorrhea‐like” symptoms are N. gonorrhoeae . Meningococcus and Neisseria lactamica have been isolated in urethritis cases, and a recent outbreak of meningococcal urethritis renewed interest in the question of whether adaptation to the urogenital niche may happen periodically . N. gonorrhoeae is not as diverse as other Neisseria (Fig.…”

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

“…Bacterial strains used in this study are listed in Table . These stains included 52 N. meningitidis urethritis clade isolates collected from men between January 2015 and September 2015 at Columbus Public Health (CPH), Columbus, Ohio (Tzeng et al ., ) with the CNM3 isolate being the major representative of this collection. The initial demographic features of these cases and the collection protocol have been previously reported (Bazan et al ., ; ).…”

“…Similar Nm‐associated urethritis clusters have now been observed in multiple US cities (Bazan et al ., ; ; Toh et al ., ; Retchless et al ., ). These urethritis‐associated Nm isolates are members of a novel nongroupable US Nm urethritis clade (US_NmUC) in the cc11/ET‐15 hyperinvasive lineage (Tzeng et al ., ). The US_NmUC isolates do not make capsules (Toh et al ., ; Tzeng et al ., ) due to an IS1301 insertion that caused a multi‐gene deletion at the capsule biosynthesis locus (Tzeng et al ., ).…”

Neisseria meningitidis urethritis: synthesis of published data

“…Neisseria meningitidis has been isolated from anogenital sites and has been documented as a cause of anogenital infection in many publications . The first report published in 1942 by Carpenter and Charles described seven isolates of NM among 103 urogenital isolates of Neisseria . Since 2015, NM was the exclusive cause of symptomatic urethritis in Columbus, Ohio (3–36% per month) and Indianapolis (2.8%, 1.4%, and 6.9% in 2013, 2014, and 2015, respectively) .…”

“…The first report published in 1942 by Carpenter and Charles described seven isolates of NM among 103 urogenital isolates of Neisseria . Since 2015, NM was the exclusive cause of symptomatic urethritis in Columbus, Ohio (3–36% per month) and Indianapolis (2.8%, 1.4%, and 6.9% in 2013, 2014, and 2015, respectively) . Since then, outbreaks of urethritis in heterosexuals and IMD in MSM have been reported .…”