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.

ObjectivesChlamydia trachomatis (CT) and Mycoplasma genitalium (MG) cause the majority of non-gonococcal urethritis (NGU). The role of Ureaplasma urealyticum (UU) in NGU is unclear. Prior case–control studies that examined the association of UU and NGU may have been confounded by mixed infections and less stringent criteria for controls. The objective of this case–control study was to determine the prevalence and aetiology of mixed infections in men and assess if UU monoinfection is associated with NGU.MethodsWe identified 155 men with NGU and 103 controls. Behavioural and clinical information was obtained and men were tested for Neisseria gonorrhoeae and CT, MG, UU and Trichomonas vaginalis (TV). Men who were five-pathogen negative were classified as idiopathic urethritis (IU).ResultsTwelve per cent of NGU cases in which a pathogen was identified had mixed infections, mostly UU coinfections with MG or CT; 27% had IU. In monoinfected NGU cases, 34% had CT, 17% had MG, 11% had UU and 2% had TV. In controls, pathogens were rarely identified, except for UU, which was present in 20%. Comparing cases and controls, NGU was associated with CT and MG monoinfections and mixed infections. UU monoinfection was not associated with NGU and was almost twice as prevalent in controls. Men in both the case and control groups who were younger and who reported no prior NGU diagnosis were more likely to have UU (OR 0.97 per year of age, 95% CI 0.94 to 0.998 and OR 6.3, 95% CI 1.4 to 28.5, respectively).ConclusionsMixed infections are common in men with NGU and most of these are UU coinfections with other pathogens that are well-established causes of NGU. UU monoinfections are not associated with NGU and are common in younger men and men who have never previously had NGU. Almost half of NGU cases are idiopathic.

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The human papillomavirus (HPV) E1--E4 protein is detected in the cytoplasm of differentiated keratinocytes, near the cornified cell envelope. HPV does not induce lysis of the infected keratinocyte, and the normally durable cornified cell envelope that forms during keratinocyte differentiation would seemingly inhibit viral egress. HPV infection induces abnormalities of the cornified cell envelope, but the exact mechanisms involved are not well understood. We tested whether the HPV 11 E1--E4 protein, which co-localizes the cell envelope and co-purifies with cell envelope fragments, could serve as an in vitro substrate for transglutaminases. We found evidence of E1--E4 cross-linking by endogenous transglutaminases in an in situ assay using frozen sections of human foreskin, and in addition, E1--E4 protein was cross-linked by recombinant transglutaminase 3 (but not transglutaminase 1) in an in vitro cross-linking assay. We also tested whether expression of E1--E4 in differentiated keratinocytes would induce morphologic alterations of cornified cell envelopes. Differentiated keratinocytes expressing E1--E4 were disorganized and pleomorphic compared to control cells, and cell envelopes purified from E1--E4-expressing cells were small, fragmented, and rough bordered compared to the round, smooth bordered cell envelopes from control cells. We conclude from these in vitro experiments that the E1--E4 protein is cross-linked by transglutaminase 3, and that E1--E4 expression in differentiated keratinocytes induces morphologic abnormalities of the cornified cell envelope.