Abstract
The obligate intracellular pathogen Chlamydia trachomatis is the leading cause of noncongenital blindness and causative agent of the most common sexually transmitted infection of bacterial origin. With a reduced genome, C. trachomatis is dependent on its host for survival, in part due to a need for the host cell to compensate for incomplete bacterial metabolic pathways. However, relatively little is known regarding how C. trachomatis is able to hijack host cell metabolism. In this study, we show that two host glycolytic enzymes, aldolase A and pyruvate kinase, as well as lactate dehydrogenase, are enriched at the C. trachomatis inclusion membrane during infection. Inclusion localization was not species specific, since a similar phenotype was observed with C. muridarum Time course experiments showed that the number of positive inclusions increased throughout the developmental cycle. In addition, these host enzymes colocalized to the same inclusion, and their localization did not appear to be dependent on sustained bacterial protein synthesis or on intact host actin, vesicular trafficking, or microtubules. Depletion of the host glycolytic enzyme aldolase A resulted in decreased inclusion size and infectious progeny production, indicating a role for host glycolysis in bacterial growth. Finally, quantitative PCR analysis showed that expression of C. trachomatis glycolytic enzymes inversely correlated with host enzyme localization at the inclusion. We discuss potential mechanisms leading to inclusion localization of host glycolytic enzymes and how it could benefit the bacteria. Altogether, our findings provide further insight into the intricate relationship between host and bacterial metabolism during Chlamydia infection.