Modulation of Host Cell Metabolism by Chlamydia trachomatis.

Abstract

Propagation of the intracellular bacterial pathogen Chlamydia trachomatis is strictly bound to its host cells. The bacterium has evolved by minimizing its genome size at the cost of being completely dependent on its host. Many of the vital nutrients are synthesized only by the host, and this has complex implications. Recent advances in loss-of-function analyses and the metabolomics of human infected versus noninfected cells have provided comprehensive insight into the molecular changes that host cells undergo during the stage of infection. Strikingly, infected cells acquire a stage of high metabolic activity, featuring distinct aspects of the Warburg effect, a condition originally assigned to cancer cells. This condition is characterized by aerobic glycolysis and an accumulation of certain metabolites, altogether promoting the synthesis of crucial cellular building blocks, such as nucleotides required for DNA and RNA synthesis. The altered metabolic program enables tumor cells to rapidly proliferate as well as C. trachomatis-infected cells to feed their occupants and still survive. This program is largely orchestrated by a central control board, the tumor suppressor protein p53. Its downregulation in C. trachomatis-infected cells or mutation in cancer cells not only alters the metabolic state of cells but also conveys the prevention of programmed cell death involving mitochondrial pathways. While this points toward common features in the metabolic reprogramming of infected and rapidly proliferating cells, it also forwards novel treatment options against chronic intracellular infections involving well-characterized host cell targets and established drugs.