Functional analysis of nonsynonymous single nucleotide polymorphisms in chlamydial tissue tropism-related genes

Gram-negative obligate intracellular pathogen, C. pneumoniae can disseminate from the lung to the vasculature by peripheral blood monocytes. Therefore, it not only causes infections of the upper and lower respiratory tract, but also associates with coronary artery disease (CAD). In our previous study, genetic analyses point towards a tissue tropism of different C. pneumoniae isolates. We showed that bacterial isolates from the respiratory tract and the vascular system share high sequence similarity and their genetic difference is solely based on a set of non-synonymous single nucleotide polymorphisms (nsSNPs). However, the underlying functional impact of nsSNP in chlamydial tissue tropism is completely unclear. In this proposal, we will elucidate functional effects of the observed nsSNPs with respect to C. pneumoniae tissue tropism using our novel genetic modification technique. We propose that functional characterization of nsSNPs will foster our pathophysiological understanding of this obligate intracellular pathogen and tissue tropism.