Orogenital Transmission of Neisseria meningitidis Causing Acute Urethritis in Men Who Have Sex with Men.
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ABSTRACT:
SUBMITTER: Jannic A
PROVIDER: S-EPMC6302579 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neisseria meningitidis, typically a resident of the oro- or nasopharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonizing the urogenital tract. This can result in urethritis, akin to the syndrome caused by its sister species, N. gonorrhoeae, the etiologic agent of gonorrhea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with the gonococcus, raising the question of the extent to which these strains contain features that promote adaptation to the genitourinary niche, making them gonococcus-like and distinguishing them from other N. meningitidis strains. Here, we analyzed the genomes of 39 diverse N. meningitidis isolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene (aniA), the factor H-binding protein gene (fHbp), and the capsule biosynthetic locus, all of which are loci previously suggested to be associated with urogenital colonization. We observed notable diversity, including frameshift variants, in aniA and fHbp and the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused by N. meningitidis are possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associated N. meningitidis strains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract.
| S-EPMC5703804 | biostudies-literature
Project description:BackgroundNeisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae.MethodsIn response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015.ResultsSeventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24-38) and had a median of 2 sex partners in the last 3 months (IQR = 1-3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52).ConclusionsBetween January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission.
| S-EPMC5848337 | biostudies-literature
Project description:At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae-negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade.
| S-EPMC5324800 | biostudies-literature
Project description:BackgroundCross-protective immunity between Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) may inform gonococcal vaccine development. Meningococcal serogroup B (MenB) outer membrane vesicle (OMV) vaccines confer modest protection against gonorrhea. However, whether urethral Nm infection protects against gonorrhea is unknown. We examined gonorrhea risk among men with US Nm urethritis clade (US_NmUC) infections.MethodsWe conducted a retrospective cohort study of men with urethral US_NmUC (n = 128) between January 2015 and April 2018. Using diagnosis date as the baseline visit, we examined Ng status at return visits to compute urethral Ng risk. We compared these data to 3 referent populations: men with urethral Ng (n = 253), urethral chlamydia (Ct) (n = 251), and no urethral Ng or Ct (n = 255). We conducted sensitivity analyses to assess varied approaches to censoring, missing data, and anatomical site of infection. We also compared sequences of protein antigens in the OMV-based MenB-4C vaccine, US_NmUC, and Ng.ResultsParticipants were primarily Black (65%) and heterosexual (82%). Over follow-up, 91 men acquired urethral Ng. Men with urethral US_NmUC had similar Ng risk to men with prior urethral Ng (adjusted hazard ratio [aHR]: 1.27; 95% CI: .65-2.48). Men with urethral US_NmUC had nonsignificantly increased Ng risk compared with men with urethral Ct (aHR: 1.51; 95% CI: .79-2.88), and significantly increased Ng risk compared with men without urethral Ng or Ct (aHR: 3.55; 95% CI: 1.27-9.91). Most of the protein antigens analyzed shared high sequence similarity.ConclusionsUrethral US_NmUC infection did not protect against gonorrhea despite substantial sequence similarities in shared protein antigens.
| S-EPMC9258932 | biostudies-literature
Project description:During 2003-2012, 8 clusters of meningococcal disease were identified in Rio de Janeiro State, Brazil, all caused by serogroup C Neisseria meningitidis. The isolates were assigned to 3 clonal complexes (cc): cc11, cc32, and cc103. These hyperinvasive disease lineages were associated with endemic disease, outbreaks, and high case-fatality rates.
| S-EPMC3837672 | biostudies-literature
Project description:Changing antigenic structure such as with capsule polysaccharide is a common strategy for bacterial pathogens to evade a host immune system. The recent emergence of an invasive W:2a:P1.7-2,4 sequence type 11 (ST-11) strain of Neisseria meningitidis in New Zealand, an uncommon serogroup/serotype in New Zealand disease cases, was investigated for its genetic origins. Molecular typing of 107 meningococcal isolates with similar serotyping characteristics was undertaken to determine genetic relationships. Results indicated that the W:2a:P1.7-2,4 strain had emerged via capsule switching from a group C strain (C:2a:P1.7-2,4). Neither the upstream nor downstream sites of recombination could be elucidated, but sequence analysis demonstrated that at least 45 kb of DNA was involved in the recombination, including the entire capsule gene cluster. The oatWY gene carried by the W:2a:P1.7-2,4 strain contained the insertion sequence element IS1301, one of five variants of oatWY found in group W135 strains belonging to the carriage-associated ST-22 clonal complex. This suggested that the origin of the capsule genes carried by the invasive W:2a:P1.7-2,4 strain is carriage associated. These results provide novel evidence for the long-standing dogma that disease-associated strains acquire antigenic structure from carriage-associated strains. Moreover, the capsule switch described here has arisen from the exchange of the entire capsule locus.
| S-EPMC2708544 | biostudies-literature
Project description:BackgroundIncreased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the "U.S. NmNG urethritis clade". Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015.ResultsThe earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected.ConclusionsInterspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the frequency with which it causes urethritis.
| S-EPMC5834837 | biostudies-literature
Project description:Neisseria meningitidis (Nm) is a bacterial pathogen responsible for invasive meningococcal disease. Though typically colonizing the nasopharynx, multiple outbreaks of meningococcal urethritis were first reported in 2015-2016; outbreaks originally presumed to be caused by Neisseria gonorrhoeae (Ng). Genomic analysis revealed that the Nm isolates causing these outbreaks were a distinct clade, and had integrated gonococcal DNA at multiple genomic sites, including the gonococcal denitrification apparatus aniA-norB, a partial gonococcal operon of five genes containing ispD, and the acetylglutamate kinase gene argB with the adjacent gonococcal locus NGO0843. The urethritis isolates had also deleted the group C capsule biosynthesis genes cssA/B/C and csc, resulting in loss of capsule. Collectively, these isolates form the N. meningitidis urethritis clade (NmUC). Genomic analysis of recent (2016-2022) NmUC isolates revealed that the genomic features have been maintained in the clade, implying that they are important for NmUC's status as a urogenital pathogen. Furthermore, the analysis revealed the emergence of a sub-clade, designated NmUC-B, phylogenetically separated from the earlier NmUC-A. This sub-clade has integrated additional gonococcal alleles into the genome, including alleles associated with antimicrobial resistance. NmUC continues to adapt to a urethral niche and evolve as a urogenital pathogen.
| S-EPMC10634446 | biostudies-literature
Project description:BackgroundNeisseria meningitidis (Nm) is a pathogen of multiple serogroups that is highly prevalent in many populations. Serogroups associated with invasive meningococcal disease (IMD) in Canada, for example, include A, B, C, W-135, X and Y. IMD is a rare but serious outcome of Nm infection, and can be prevented with vaccines that target certain serogroups. This has stimulated the development of dynamic models to evaluate vaccine impact. However, these models typically aggregate the various Nm serogroups into a small number of combined groups, instead of modelling each serogroup individually. The impact of aggregation on dynamic Nm model predictions is poorly understood. Our objective was to explore the impact of aggregation on dynamic model predictions.MethodsWe developed two age-structured agent-based models--a 2-strain model and a 4-strain model--to simulate vaccination programs in the Canadian setting. The 2-strain model was used to explore two different groupings: C, versus all other serogroups combined; and B, versus all other serogroups combined. The 4-strain model used the four groupings: C, B, Neisseria lactamica, versus all other serogroups combined. We compared the predicted impact of monovalent C vaccine, quadrivalent ACWY vaccine (MCV-4), and monovalent B vaccine (4CMenB) on the prevalence of serogroup carriage under these different models.ResultsThe 2-strain and 4-strain models predicted similar overall impacts of vaccines on carriage prevalence, especially with respect to the vaccine-targeted serogroups. However, there were some significant quantitative and qualitative differences. Declines in vaccine-targeted serogroups were more rapid in the 2-strain model than the 4-strain model, for both the C and the 4CMenB vaccines. Sustained oscillations, and evidence for multiple attractors (i.e., different types of dynamics for the same model parameters but different initial conditions), occurred in the 4-strain model but not the 2-strain model. Strain replacement was also more pronounced in the 4-strain model, on account of the 4-strain model spreading prevalence more thinly across groups and thus enhancing competitive interactions.ConclusionsSimplifying assumptions like aggregation of serogroups can have significant impacts on dynamic model predictions. Modellers should carefully weigh the advantages and disadvantages of aggregation when formulating models for multi-strain pathogens.
| S-EPMC4520071 | biostudies-literature
Project description:Clusters of Neisseria meningitidis (Nm) urethritis among primarily heterosexual males in multiple US cities have been attributed to a unique non-encapsulated meningococcal clade (the US Nm urethritis clade, US_NmUC) within the hypervirulent clonal complex 11. Resistance to antimicrobial peptides (AMPs) is a key feature of urogenital pathogenesis of the closely related species, Neisseria gonorrhoeae. The US_NmUC isolates were found to be highly resistant to the model AMP, polymyxin B (PmB, MICs 64-256 µg ml-1 ). The isolates also demonstrated stable subpopulations of heteroresistant colonies that showed near total resistant to PmB (MICs 384-1024 µg ml-1 ) and colistin (MIC 256 µg ml-1 ) as well as enhanced LL-37 resistance. This is the first observation of heteroresistance in N. meningitidis. Consistent with previous findings, overall PmB resistance in US_NmUC isolates was due to active Mtr efflux and LptA-mediated lipid A modification. However, whole genome sequencing, variant analyses and directed mutagenesis revealed that the heteroresistance phenotypes and very high-level AMP resistance were the result of point mutations and IS1655 element movement in the pilMNOPQ operon, encoding the type IV pilin biogenesis apparatus. Cross-resistance to other classes of antibiotics was also observed in the heteroresistant colonies. High-level resistance to AMPs may contribute to the pathogenesis of US_NmUC.
| S-EPMC6351203 | biostudies-literature