Tuesday, December 18, 2012

Fierce competition between Toxoplasma and Chlamydia for host cell structures in dually infected cells

Eukaryot Cell. 2012 Dec 14. [Epub ahead of print]

Fierce competition between Toxoplasma and Chlamydia for host cell structures in dually infected cells

Romano JD, de Beaumont C, Carrasco JA, Ehrenman K, Bavoil PM, Coppens I

Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA

The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to 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 co-infected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in co-infected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our co-infection studies by examining the respective abilities of Chlamydia and Toxoplasma to 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, Toxoplasma out-competes Chlamydia to the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected with Chlamydia, the centrosomes become associated with the chlamydial inclusion while the Toxoplasma parasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by both Chlamydia and Toxoplasma depends 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.

 PMID: 23243063 [PubMed - as supplied by publisher]

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