Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for various human diseases including trachoma, genital tract... Show moreChlamydia trachomatis is an obligate intracellular bacterium that is responsible for various human diseases including trachoma, genital tract infections, and lymphogranuloma venereum. Energy metabolism consists many essential pathways to generate energy for every organism. However, it remains much unknown in C. trachomatis. For decades, C. trachomatis has been considered as an “energy parasite”, which needs the energy supply from the host cells entirely. In contrast, genomic studies show that this bacterium is capable of encoding enzymes that involve energy metabolism. However, no experimental data were provided to support the genomic information due to the peculiar developmental cycle of C. trachomatis inside the host cells. In this project, the oxidative phosphorylation pathway of C. trachomatis is first identified with experimental results. This pathway starts with the sodium pumping NADH:Ubiquinone oxidoreductase enzyme complex (NQR) transferring the electrons along the respiratory chain and generating a sodium gradient across the membrane. C. trachomatis contains an A-type ATPase that can utilize this sodium gradient to generate ATP. In vitro experiments in mammalian cells with different respiratory inhibitors show that C. trachomatis is not an obligate energy parasite. Instead, it has a dynamic energy dependency on the host metabolism that the bacterium switches from entirely to partially relying on the host energy metabolism for its energy requirement. The sodium gradient established by NQR and/or other transporters is of great importance to chlamydial metabolism. Further, the respiratory inhibitors test on interferon-γ-induced persistence of C. trachomatis in mammalian cell cultures shows that an inhibited energy metabolism prevents and eliminates the persistent form. This study provides new insights about antibiotics development and therapeutic methods against C. trachomatis infections. Show less
