Host Organelle Hijackers: a similar modus operandi for Toxoplasma gondii and Chlamydia trachomatis: co-infection model as a tool to investigate pathogenesis

Abstract

The bacterium Chlamydia trachomatis and the protozoan parasite Toxoplasma gondii are the causative agents of chlamydiosis and toxoplasmosis in humans, respectively. Both microorganisms are obligate intracellular pathogens and notorious for extensively modifying the cytoskeletal architecture and the endomembrane system of their host cells to establish productive infections. This review highlights the similar tactics developed by these two pathogens to manipulate their host cell despite their genetic unrelatedness. Using an in vitro cell culture model whereby single fibroblasts are infected by C. trachomatis and T. gondii simultaneously, thus setting up an intracellular competition, we demonstrate that the solutions to the problem of intracellular survival deployed by the parasite and the bacterium may represent an example of convergent evolution, driven by the necessity to acquire nutrients in a hostile environment.

Keywords: bacteria; convergent evolution; host organelle interaction; intracellular parasitism; nutrient scavenging; protozoa.

Figure 1. Model for the interaction of Toxoplasma gondii with host cells

A schematic representation of the PV and the host cell structures that are recruited by the parasite is shown. These host cell-PV interactions are illustrated by immunofluorescence and electron microscopy images. Host structures are indicated by an arrow. The following antibodies and dyes used for staining are: anti-γ-tubulin for MTOC (green) and anti-GRA7 for the PV membrane (red); anti-giantin for Golgi (green) and anti-GRA7 (red); anti-α-tubulin for microtubules in a multi-infected cell; anti-calnexin for ER, anti-SAG1 for the parasite plasma membrane and DAPI for nuclei; mito-Tracker for mitochondria and DAPI; Texas-red EGF (red) for endo-lysosomes and anti-α-tubulin (green). EM picture shows an endocytic organelle containing LDL-gold particles. Scale bars are 150 nm.

Figure 2. Model for the interaction of Chlamydia trachomatis with host cells

A schematic representation of an inclusion and host cell structures that are recruited by the bacterium is shown. These host cell-inclusion interactions are illustrated by immunofluorescence images. Host structures are indicated by an arrow. The following antibodies and dyes used for staining are: anti-γ-tubulin for MTOC (green) and anti-EF-Tu for Chlamydia (red); Nile Red for lipid bodies (yellow) and DAPI; anti-giantin for Golgi (green) and DAPI; anti-α-tubulin for microtubules and DAPI; anti-calnexin for ER and DAPI; anti-CERT for ER-derived vesicles (green) and anti-EF-Tu (red); anti-CD-63 for multivesicular bodies (red) and DAPI; Nile Red for lipid bodies (yellow) and DAPI. Inc, inclusion; hnu, host nucleus.

Figure 3. Co-infection of mammalian cells with Toxoplasma gondii and Chlamydia trachomatis, and host cell interactions with the PV and the inclusion during co-infection

A. A phase and immunofluorescence image of a mono- and a co-infected epithelial cellsshowing the poor development of the inclusion (stained for EF-Tu in green; arrow) during a 24-h co-infection while the parasites (stained for GRA7 in red) develop normally. Both the inclusion and the PV are located in the perinuclear region of the host cell. Scale bar is 10 µm. B. A schematic representation of a PV and an inclusion occupying the same cell for 24-h summarizing their interaction with host cell structures. Similarly as in a mono-infection, the PV is anchored to the host nuclear envelope, associates with the host MTOC, microtubules, ER, mitochondria and attracts host Golgi fragments and endocytic organelles (in red) that are further delivered into the PV. In contrast, inclusions growing in a PV-containing cell shift to a stress-induced persistence state with large aberrant bodies despite its association with host microtubules (in the absence of the MTOC), Golgi fragments, ER and CERT vesicles, and the presence of lipid bodies in the vacuole.