Fierce Competition between Toxoplasma and Chlamydia for Host Cell Structures in Dually Infected Cells

Abstract

ABSTRACTThe prokaryoteChlamydia trachomatisand the protozoanToxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similarmodus operandito colonize their host cell and salvage nutrients from organelles. In order to gain fundamental knowledge on the pathogenicity of these microorganisms, we have established a cell culture model whereby single fibroblasts are coinfected byC. trachomatisandT. gondii. We previously reported that the two pathogens compete for the same nutrient pools in coinfected cells and thatToxoplasmaholds a significant competitive advantage overChlamydia. Here we have expanded our coinfection studies by examining the respective abilities ofChlamydiaandToxoplasmato co-opt the host cytoskeleton and recruit organelles. We demonstrate that the two pathogen-containing vacuoles migrate independently to the host perinuclear region and rearrange the host microtubular network around each vacuole. However,ToxoplasmaoutcompetesChlamydiato the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected withChlamydia, the centrosomes become associated with the chlamydial inclusion, while theToxoplasmaparasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi apparatus and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by bothChlamydiaandToxoplasmadepends on the capability of each pathogen to successfully adhere to a finely tuned developmental program that aims to remodel the host cell for the pathogen's benefit. In particular, this investigation emphasizes the essentiality of host organelle interception by intravacuolar pathogens to facilitate access to nutrients.