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Chlamydia trachomatis utilizes the host cell microtubule network during early events of infection
J D Clausen1, G Christiansen, H U Holst
1Department of Medical Microbiology, University of Aarhus, Aarhus C, Denmark.
Abstract:
The 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 Chlamydia-containing 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 phosphorylation of HeLa cell proteins during uptake than that seen for C. trachomatis.
Insights
Chlamydia trachomatis utilizes host cell microtubules and dynein for intracellular trafficking, impacting infectivity. Chlamydia pneumoniae shows different cytoskeletal requirements during early infection.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- The host cell cytoskeleton is crucial for intracellular pathogen invasion and movement.
- Microtubules and motor proteins facilitate pathogen trafficking within host cells.
Purpose of the Study:
- To investigate the role of the host cell cytoskeleton, specifically microtubules and dynein, in the intracellular migration and infectivity of Chlamydia trachomatis.
- To compare the cytoskeletal requirements of Chlamydia trachomatis with Chlamydia pneumoniae during early infection stages.
Main Methods:
- Indirect immunofluorescence microscopy to visualize microtubule and Chlamydia vesicle colocalization.
- Inhibition of host cell dynein to assess its effect on Chlamydia trachomatis infectivity.
- Analysis of tyrosine phosphorylation in host cells upon infection with different Chlamydia species.
Main Results:
- Chlamydia trachomatis vesicles colocalized with microtubules and tyrosine-phosphorylated proteins during migration to a perinuclear location.
- Chlamydia-containing vesicles were found at the center of the microtubule network, indicating microtubule-dependent redistribution.
- Dynein inhibition significantly affected Chlamydia trachomatis infectivity, and dynein colocalized with Chlamydia trachomatis but not Chlamydia pneumoniae aggregates.
- Chlamydia trachomatis induced more host cell tyrosine phosphorylation during uptake than Chlamydia pneumoniae.
Conclusions:
- Chlamydia trachomatis relies on microtubule-dependent intracellular transport mediated by dynein for early infection events.
- Chlamydia pneumoniae exhibits distinct cytoskeletal requirements compared to Chlamydia trachomatis, suggesting different host-pathogen interaction mechanisms.