As the leading sexually-transmitted bacterial pathogen (over 100 million people infected annually worldwide), the obligated intracellular bacterium Chlamydia trachomatis is a human pathogen of immense clinical and societal importance. Given the impact of C. trachomatis on human health, there is great interest in understanding the molecular mechanism underlying its pathogenesis for the improvement of vaccine development and antimicrobial drug discovery. Members of the Chlamydiae phylum are obligate intracellular pathogens that have evolved to become depended upon the host for most of their metabolic needs. Because of this obligated intracellular life, the bacteria not only has shrunk its genome down to just over 900 genes but also been historically refractory to genetic manipulation. Even when the bacteria co-oped its host for metabolic resources, there are still a few biosynthesis pathways conserved within its genome suggesting the importance of those metabolites. Through mechanistic enzymology bioinformatics tools like sequence similarity networks, we have mapped the chlamydial genes involved in the biosynthesis of menaquinone, the central electron shuttle in chlamydial respiration, via the recently discovered futalosine pathway. Although the current proposed futalosine pathway still missing the final key steps, we have identified the potential chlamydial genes that complete it based on similarity to the traditional menaquinone biosynthesis pathway found in Escherichia coli. We have successfuly solved the structure of one of those enzymes, the chlamydial CT220 protein - a UbiX homolog. Utilizing enzymatic and structural studies together with newly developed mutagenesis methods for Chlamydia trachomatis, we aim to validate the mechanism as well as essentiality of the identified enzymes within the context of Chlamydia infection.

Examination of essential genes involved in the biosynthesis of key metabolite by Chlamydia trachomatis

253rd National Meeting (2017)

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