The Centers for Disease Control and Prevention (CDC) have reported that these infections result in an annual cost to Americans of over $10 billion. In the United States alone, more than 1 million cases are reported each year, although the actual rates are estimated to be 2.8 million due to the deficiencies in screening and reporting ( 2). Over 92 million individuals are infected with C. trachomatis in the urogenital tract annually ( 1). C. trachomatis is the leading cause of preventable blindness in tropical developing countries and the leading global cause of bacterial sexually transmitted diseases (STDs) ( 1).
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.Ĭhlamydia trachomatis is responsible for a broad spectrum of diseases in males and females of all age groups worldwide. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. Bioinformatic and statistical analyses identified the strain as a recombinant of L 2 and D strains with highly conserved clustered regions of genetic exchange. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. Lymphogranuloma 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). Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation. While recombination has been known to occur for C. trachomatis based 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. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Deep genome sequencing revealed that L 2c was a recombinant of L 2 and 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. L 2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. We characterized an unusual LGV strain, termed L 2c, isolated from an MSM with severe hemorrhagic proctitis.
Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L 2/434 and outbreak strain L 2b/UCH-1/proctitis. 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. Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide.