Using proteomics to unravel tissue tropism for human chlamydia species

Award amount: 40,000.00

Chlamydia pneumoniae and Chlamydia trachomatis are obligate intracellular bacterial pathogens that are important causes of human infections for which no vaccine exists. C. pneumoniae is responsible for ~10% of respiratory tract infections. C. trachomatis serovars D-K are the leading cause of bacterial sexually transmitted infections and preventable infertility in the US. Serovars A-C are associated with trachoma, the leading cause of non-congenital blindness in developing nations. Despite the specific diseases and tissue tropism observed among Chlamydia species, these pathogens exhibit remarkable genomic synteny and identity, yet, we do not understand why these closely related species cause such distinct diseases. Candidate Chlamydial proteins that may account for distinct diseases and tissue tropism are a class of effectors called the inclusion membrane proteins (Incs). Incs are inserted into the parasitophorous inclusion membrane in which Chlamydia replicate, where they interface with host proteins. While some Incs are highly conserved between Chlamydia 3 species, others are unique among species or serovars. We hypothesize that Inc-host cell interactions are key determinants of the pathogenesis and tissue tropism of human Chlamydial diseases. We recently applied a high throughput affinity purification/mass spectrometry (AP-MS) approach, in conjunction with bioinformatics, to identify host binding partners of C. trachomatis Inc proteins to determine their biological function. Aim 1: We will utilize AP-MS to identify species- and serovar-specific Inc-host interactions for C. pneumoniae and C. trachomatis ocular and urogenital isolates. Aim 2: We will perform bioinformatics analysis of the AP-MS data sets to identify high confidence Inc-host interactions, which will identify unique pathogenic strategies utilized by C. pneumoniae and C. trachomatis and may elucidate interactions responsible for tissue tropism. These aims will allow us to develop a species specific-host protein-protein interaction map and guide future studies to characterize the mechanisms by which Chlamydiae subvert unique host processes to cause specific diseases.