title: Emergence of a newNeisseria meningitidisclonal 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 capsulectr-cssoperons and adjacent deletion ofcssA/B/Cand a part ofcsc, 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 thecpslocus. Surprisingly, these isolates had acquired by gene conversion the complete gonococcal denitrificationnorB-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 theNeisseria gonorrheae norB-aniAcassette promoting anaerobic growth.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Yih-Ling
authors.initials: YL
authors.lastname: Tzeng
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, OH 43210.|Sexual Health Clinic, Columbus Public Health, Columbus, OH 43210.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Bazan
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, OH 43210.
authors.forename: Abigail Norris
authors.initials: AN
authors.lastname: Turner
authors.affiliation: Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Meningitis and Vaccine Preventable Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Retchless
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Read
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Toh
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.
authors.forename: David E
authors.initials: DE
authors.lastname: Nelson
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322.|Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322.
authors.forename: Carlos
authors.initials: C
authors.lastname: Del Rio
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322; dstep01@emory.edu.|Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: David S
authors.initials: DS
authors.lastname: Stephens
mesh_terms: D002999:Clone Cells; D006801:Humans; D008297:Male; D008585:Meningitis, Meningococcal / Q000453:epidemiology* / Q000235:genetics / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D065288:Serogroup; D014481:United States / Q000453:epidemiology; D000073336:Whole Genome Sequencing
keywords: IS1301; Neisseria meningitidis; capsule; denitrification; meningococcal urethritis