Chlamydial infection induces host cytokinesis failure at abscission

Abstract

Chlamydia trachomatis is an obligate intracellular bacteria and the infectious agent responsible for the sexually transmitted disease Chlamydia. Infection with Chlamydia can lead to serious health sequelae such as pelvic inflammatory disease and reproductive tract scarring contributing to infertility and ectopic pregnancies. Additionally, chlamydial infections have been epidemiologically linked to cervical cancer in patients with a prior human papilomavirus (HPV) infection. Chlamydial infection of cultured cells causes multinucleation, a potential pathway for chromosomal instability. Two mechanisms that are known to initiate multinucleation are cell fusion and cytokinesis failure. This study demonstrates that multinucleation of the host cell by Chlamydia is entirely due to cytokinesis failure. Moreover, cytokinesis failure is due in part to the chlamydial effector CPAF acting as an anaphase promoting complex mimic causing cells to exit mitosis with unaligned and unattached chromosomes. These lagging and missegregated chromosomes inhibit cytokinesis by blocking abscission, the final stage of cytokinesis.

Post-Translational Control of IL-1β via the Human Papillomavirus Type 16 E6 Oncoprotein: A Novel Mechanism of Innate Immune Escape Mediated by the E3-Ubiquitin Ligase E6-AP and p53

“…Studies in caspase-1 knock-out mice have shown that these animals have an increased susceptibility to a variety of infections, because IL-1β maturation is impaired [17]. Conversely, caspase-1 seems not to be involved in the immune surveillance against Chlamydia trachomatis [76], since its activity is even required for efficient and optimal growth of chlamydial inclusions in cervical epithelial cells [77] This aspect is interesting especially in the context of an epidemiologically significant association between Chlamydia infection, persisting HPV and the development of cervical cancer [78]. Hence, our finding that a similar caspase-1 activity can be observed within all immortalized cells independent of which viral oncoprotein is expressed (Fig.…”

Chlamydia trachomatis Inclusion Disrupts Host Cell Cytokinesis to Enhance Its Growth in Multinuclear Cells

“…It has been well documented that C. trachomatis infection can lead to host cell multinucleation by disrupting host cytokinesis through disruption of furrow ingression or abscission [Greene and Zhong, ; Sun et al, ; Brown et al, ]. Moreover, a recent study has shown that C. muridarum can infect actively replicating host cells in a mouse model [Knowlton et al, ].…”

Fierce Competition between Toxoplasma and Chlamydia for Host Cell Structures in Dually Infected Cells

“…Another factor that may contribute to the stress-induced persistent state of C. trachomatis during coinfection may be the failure to associate with the host MTOC by the inclusion. Many studies report that C. trachomatis modifies the host cell cycle by selectively targeting different cellular pathways (10,60,61). Although a potential selective advantage for Chlamydia in recruiting host centrosomes has not been demonstrated, it is possible to speculate that by stalling host cell division before cytokinesis, the bacterium ensures for itself a stable and spacious environment, sufficient to sustain its developmental cycle.…”