Abstract
The cellular exit strategies of intracellular pathogens have a direct impact on microbial dissemination, transmission, and engagement of immune responses of the host. Chlamydia exit their host via a budding mechanism called extrusion, which offers protective benefits to Chlamydia as they navigate their extracellular environment. Many intracellular pathogens co-opt cellular abscission machinery to facilitate cell exit, which is utilized to perform scission of two newly formed daughter cells following mitosis. Similar to viral budding exit strategies, we hypothesize that an abscission-like mechanism is required to physically sever the chlamydial extrusion from the host cell, co-opting the membrane fission activities of the endosomal sorting complex required for transport (ESCRT) family of proteins that are necessary for cellular scission events, including abscission. To test this, C. trachomatis L2-infected HeLa cells were depleted of key abscission machinery proteins charged multivesicle body protein 4b (CHMP4B), ALIX, centrosome protein 55 (CEP55), or vacuolar protein sorting-associated protein 4A (VPS4A), using RNA interference (RNAi). Over 50% reduction in extrusion formation was achieved by depletion of CHMP4B, VPS4A, and ALIX, but no effect on extrusion was observed with CEP55 depletion. These results demonstrate a role for abscission machinery in C. trachomatis extrusion from the host cell, with ALIX, VPS4A and CHMP4B playing key functional roles in optimal extrusion release.
Highlights
Chlamydia trachomatis is an obligate intracellular bacterium that elicits a major public health burden worldwide [1,2]
Previous work demonstrated that the extrusion exit mechanism of Chlamydia harbored mechanistic, kinetic, and morphological similarities with the abscission stage of cellular cytokinesis [3]
The endosomal sorting complex required for transport (ESCRT) accessory proteins ALIX and Tumor Suppressor Gene 101 (TSG101) have been shown to be recruited to the midbody of the cellular intercellular bridge through interactions with centrosome protein 55 (CEP55) [28]
Summary
Chlamydia trachomatis is an obligate intracellular bacterium that elicits a major public health burden worldwide [1,2]. C. trachomatis exits host cells by two mutually exclusive pathways that are dependent on distinct host-based mechanisms: extrusion and lysis [3]. The identity of the cellular machinery that function downstream of this stage, to sever the fully formed extrusion from the host cell membrane, remains to be defined. These data, coupled with the previously described disruptive effects of C. trachomatis infection on cell division, points to a mechanism whereby host cell division signaling pathways are hijacked by Chlamydia to facilitate escape from its intracellular niche [7,8,9,10]
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