The obligate intracellular pathogen Chlamydia trachomatis is the causative agent of the blinding trachoma and the world's leading cause of bacterial sexually transmitted infections. Despite aggressive antibacterial control measures, C. trachomatis infections have been increasing, constituting a serious public health concern due to its morbidity and socioeconomic burden. Still, very little is known about the molecular basis underlying the phenotypic disparities observed among C. trachomatis serovars in terms of tissue tropism (ocular conjunctiva, epithelial-genitalia and lymph nodes), virulence (disease outcomes) and ecological success. This is in part due to the inexistence of straightforward tools to genetically manipulate Chlamydiae and host cell-free growth systems, hampering the elucidation of the biological role of loci. The recent release of tenths of full-genome C. trachomatis sequences depict a strains clustering scenario reflecting the organ/cell-type that they preferentially infect. However, the high degree of genomic conservation implies that few genetic features are involved in phenotypic dissimilarities. The purpose of this review is to gather the most relevant data dispersed throughout the literature concerning the genotypic evidences that support niche-specific phenotypes. This review focus on chromosomal dynamics phenomena like recombination and point-mutations, essentially involving outer and inclusion membrane proteins, type III secretion effectors, and hypothetical proteins with unknown function. The scrutiny of C. trachomatis loci involved in tissue tropism, pathogenesis and ecological success is crucial for the development of disease-specific prophylaxis.
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