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

Eukaryot Cell. 2013 Feb;12(2):265-77. doi: 10.1128/EC.00313-12. Epub 2012 Dec 14.

Abstract

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 coinfected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in coinfected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our coinfection 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 outcompetes 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 apparatus 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cells, Cultured
  • Centrosome / metabolism
  • Centrosome / microbiology
  • Centrosome / parasitology
  • Ceramides / metabolism
  • Chlamydia / physiology*
  • Chlamydia Infections / microbiology*
  • Chlamydia Infections / parasitology
  • Chlamydia Infections / pathology
  • Coinfection
  • Fibroblasts / microbiology
  • Fibroblasts / parasitology
  • Fibroblasts / pathology
  • Golgi Apparatus / microbiology
  • Golgi Apparatus / parasitology
  • Golgi Apparatus / pathology
  • Host-Parasite Interactions
  • Host-Pathogen Interactions
  • Humans
  • Intracellular Membranes / metabolism
  • Intracellular Membranes / microbiology
  • Intracellular Membranes / parasitology
  • Microbial Viability
  • Microtubules / metabolism
  • Microtubules / microbiology
  • Microtubules / parasitology
  • Mitochondria / microbiology
  • Mitochondria / parasitology
  • Mitochondria / pathology
  • Toxoplasma / physiology*
  • Toxoplasmosis / microbiology
  • Toxoplasmosis / parasitology*
  • Toxoplasmosis / pathology
  • Vacuoles / microbiology
  • Vacuoles / parasitology

Substances

  • Ceramides