Chlamydia trachomatis (CT) is the leading cause of preventable blindness (trachoma) and sexually transmitted diseases (STD) worldwide. While much has been learned about human chlamydial infections in the last decades, we are still lacking a complete understanding of the pathogenesis of CT diseases, and do not have an appropriate tool for precisely typing CT strains both for molecular epidemiologic and basic research studies. The major outer membrane protein (MOMP) of CT is an immunodominant protein and the primary target for serotyping, and hence strain typing along with the ompA gene, which encodes MOMP. Yet, MOMP does not fully reflect the phylogeny of the organism or distinguish strains by biologic or phenotypic properties. Other genes/proteins that may contribute to phylogeny, or these properties include the inter-genic region (IGR), polymorphic membrane proteins (Pmps), cytotoxin genes in the replication termination region (RTR) or """"""""plasticity zone"""""""", partial tryptophan operon proteins (TrpB/A), Type III secretion system proteins, chlamydial protease- or proteasome-like activity factor (CPAF), and the porin protein, PorB. Further, the majority of research on CT has used laboratory-adapted strains that may not reflect current clinical isolates that are responsible for the myriad of CT diseases described today. Our goal is to advance the genetic discovery initiated by the CT genome sequences of serovars D and L2 and other genomes of the family Chlamydiaceae by providing genome sequences of six of the 13 remaining reference serovars along with genomes of recent clinical isolates to advance our understanding of CT tissue tropism, virulence, disease pathogenesis, and evolution. Within the context of our Specific Aims, we will develop and make publicly available the data and research tools described: 1) Sequence six genomes of the remaining 13 reference serovars of CT and four genomes of selected recent clinical isolates (see #2), and develop a multi-locus sequence typing (MLST) scheme for global epidemiologic studies; MLST screening of the seven remaining reference serovars and -500 isolates from CT STD and trachoma populations worldwide will fine-tune the MLST and identify unique clinical isolates for additional genome sequencing; 2) Develop a Chlamydia GeneChip for rapid, robust genotyping of CT based on genome data and MLST findings; and 3) Develop a strain identification database to address specific research questions related to unraveling the association between genetic determinants and tissue tropism, virulence, and disease outcome in addition to the evolution of the organism and how new strain types might evolve over time. ? ?
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