Chlamydia trachomatis utilizes the host cell microtubule network during early events of infection

Abstract

SummaryThe host cell cytoskeleton is known to play a vital role in the life cycles of several pathogenic intracellular microorganisms by providing the basis for a successful invasion and by promoting movement of the pathogen once inside the host cell cytoplasm. McCoy cells infected with Chlamydia trachomatis serovars E or L2 revealed, by indirect immunofluorescence microscopy, collocation of microtubules and Chlamydia-containing vesicles during the process of migration from the host cell surface to a perinuclear location. The vast majority of microtubule-associated Chlamydia vesicles also collocated with tyrosine-phosphorylated McCoy cell proteins. After migration, the Chlamydiacontaining vesicles were positioned exactly at the centre of the microtubule network, indicating a microtubule-dependent mode of chlamydial redistribution. Inhibition of host cell dynein, a microtubule-dependent motor protein known to be involved in directed vesicle transport along microtubules, was observed to have a pronounced effect on C. trachomatis infectivity. Furthermore, dynein was found to collocate with perinuclear aggregates of C. trachomatis E and L2 but not C. pneumoniae VR-1310, indicating a marked difference in the cytoskeletal requirements for C. trachomatis and C. pneumoniae during early infection events. In support of this view, C. pneumoniae VR-1310 was shown to induce much less tyrosine phosphor ylation of HeLa cell proteins during uptake than that seen for C. trachomatis.

Molecular Dissection of Internalization of Porphyromonas gingivalis by Cells using Fluorescent Beads Coated with Bacterial Membrane Vesicle

“…It is known that taxol does not inhibit motordependent processes. Internalizations of Campylobacter jejuni (Hu and Kopecko, 1999) and Chlamydia trachomatis (Clausen et al, 1997), both of which require a dynein motor, were not prevented by taxol. On the contrary, the MVs-coated bead internalization was inhibited by both nocodazole and taxol.…”

Chlamydial Intracellular Survival Strategies

“…Soon after entry, nascent inclusions are transported along microtubules to the microtubule organizing center (MTOC) in a dynein-dependent but dynactin-independent manner (Clausen et al 1997;Grieshaber et al 2003;Grieshaber et al 2006), suggesting that one or more unknown bacterial effectors mimic the cargobinding activity of dynactin and tether the inclusion to dynein and/or to centrosomes. Src family kinases are required in human-adapted Chlamydia strains for inclusions to migrate to the MTOC and for intracellular growth, even though they are dispensable for binding and entry (Mital and Hackstadt 2011).…”

Localized Exocytosis of Primary (Lysosomal) Granules During Phagocytosis: Role of Ca2+-Dependent Tyrosine Phosphorylation and Microtubules

“…This displacement is of likely relevance for the formation of receptor signaling complexes and the activation of tyrosine phosphorylation events (50). Also, during ingestion of Chlamydiae, tyrosine phosphorylation of host cell proteins is required to trigger a microtubule-dependent redistribution of the microorganism (51). Of note, phosphorylation of tyrosine residues on tubulin (52), as well as tubulin tyrosination (53), are felt to be important in microtubule remodelling.…”