Hypervirulent Chlamydia trachomatis Clinical Strain Is a Recombinant

ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating dis-eases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains amongmen 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 anMSMwith severe hemorrhagic proctitis. L2c developed non-fusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome se-quencing revealed that L2c was a recombinant of L2 and D strains with conserved clustered regions of genetic exchange, includ-ing a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, in-clusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or pro-tein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomati