Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant between Lymphogranuloma Venereum (L2) and D Lineages

ABSTRACTChlamydia trachomatisis an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in anftsKgene promoter and in thetarpandhctBgenes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting thein vitroand disease phenotypes. While recombination has been known to occur forC. trachomatisbased on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stableC. trachomatismutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation.IMPORTANCELymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L2and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.

Nauja formalino aplikacijos gydant radiacinį hemoraginį proktitą metodika

Narimantas Evaldas SamalavičiusVilniaus universiteto Onkologijos instituto Chirurgijos klinika, Santariškių g. 1, LT-08406 VilniusEl paštas: [email protected] Radiacinis hemoraginis proktitas yra dėl spindulinio gydymo atsiradę tiesiosios žarnos pokyčiai, pasireiškiantys pogleivio fibroze ir obliteruojančiu endarteritu; išsivysčiusi talangiektazinė gleivinės neovaskuliarizacija lemia gleivinės trapumą ir polinkį kraujuoti. Esama įvairių radiacinio hemoraginio proktito gydymo metodikų. Pastaruoju metu efektyviausi literatūroje aprašomi metodai yra formalino aplikacija ir argono plazmos koaguliacija. Formalino aplikacija yra paprastas, pigus ir saugus gydymo būdas. Šiame straipsnyje pateikiamas naujas radiacinio hemoraginio proktito gydymo būdas – formalino aplikacijos. Pagrindiniai žodžiai: radiacinis proktitas, kraujavimas, formalino aplikacijaNew method of formalin application for the treatment of hemorrhagic radiation proctitis Narimantas Evaldas SamalavičiusVilnius University, Institute of Oncology, Clinic of Surgery,Santariškių str. 1, LT-08406 Vilnius, LithuaniaE-mail: [email protected] Radiation-induced hemorrhagic proctitis is a complication of radiotherapy for pelvic malignancies, which is caused by submucosal fibrosis, and endarteritis obliterans gives rise to telangiectatic neovasculature which is fragile and prone to bleeding. A number of treatment strategies of hemorrhagic radiation proctitis have been described. According to latest studies, formalin application and argon plasma coagulation seem to be most effective. Formalin application is a simple, inexpensive and safe method of treatment. A novel way of formalin application is described for those suffering from radiation hemorrhagic proctitis. Keywords: radiation proctitis, hemorrhage, formalin application