Abstract
ABSTRACTThe obligate intracellular bacterial pathogen Chlamydia trachomatis deploys virulence effectors to subvert host cell functions enabling its replication within a specialized membrane-bound compartment termed an inclusion. The control of the host cytoskeleton is crucial for Chlamydia uptake, inclusion biogenesis and cell exit. Here, we demonstrate how a Chlamydia effector rearranges the microtubule (MT) network by initiating organization of the MTs at the inclusion surface. We identified an inclusion-localized effector that is sufficient to interfere with MT assembly, which we named inclusion protein acting on MTs (IPAM). We established that IPAM recruits and stimulates the centrosomal protein 170 kDa (CEP170) to hijack the MT organizing functions of the host cell. We show that CEP170 is essential for chlamydial control of host MT assembly, and is required for inclusion morphogenesis and bacterial infectivity. Together, we demonstrate how a pathogen effector reprograms the host MT network to support its intracellular development.
Highlights
Chlamydiae are obligate intracellular pathogens that remain the leading bacterial cause of sexually transmitted disease worldwide and blinding trachoma in developing nations
IPAM− a Chlamydia inclusion protein acting on MTs Using confocal microscopy, we initially confirmed the arrangement of the MT network during the maturation of the inclusion in detail in HeLa cells (Fig. 1A)
centrosomal protein 170 kDa (CEP170) is essential for MT assembly, inclusion morphology and Chlamydia replication Given that CEP170 is a key determinant of MT organization during infection, we examined MT regrowth to assess the dynamics of this mechanism (Fig. 7)
Summary
Chlamydiae are obligate intracellular pathogens that remain the leading bacterial cause of sexually transmitted disease worldwide and blinding trachoma in developing nations. Adherent chlamydial elementary bodies (EBs) employ a type III secretion system (T3SS) to deliver effectors that induce the reorganization of the actin cytoskeleton, promoting membrane deformation that triggers EB uptake into target cells. Individual EBs are encapsulated within vacuoles derived from the host plasma membrane. These vacuoles are rapidly diverted from the endocytic pathway and instead traffic to the perinuclear region, where they coalesce to form a larger specialized compartment termed the inclusion. In this environment, the bacteria differentiate into reticulate bodies and replicate actively (Abdelrahman and Belland, 2005)
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