Grants and Contracts Details
Description
Grant title: Type III secretion-mediated manipulation of branched actin by intracellular Chlamydia
Abstract:
Chlamydia trachomatis is a significant concern for human health world-wide due to its prevalence and
the combined health and socioeconomic impact of acute and chronic disease. Chlamydiae are obligate
intracellular pathogens that possess the ability to modulate host-cell biology while sequestered within a
membrane-bound parasitophorous vacuole. Accumulating evidence indicates that a type III secretion
system (T3SS) represents a significant mechanism employed by chlamydiae to manipulate these
critical host cell functions. The host actin cytoskeleton and vesicular transport machinery represent
major targets for Chlamydia-mediated alterations. We have identified a novel pathway by which
intracellular chlamydiae redirect host cell vesicular trafficking. This mechanism requires the branched
actin network and at least two type III secretion effectors designated TmeA and TmeB. We propose to
address the hypothesis that these effectors differentially modulate branched actin networks to
accomplish trafficking of host-cell resources to the mature inclusion by imposing an axis of host Arp2/3
activation. We propose to elucidate molecular details by which the combined activities of C. trachomatis
TmeA and TmeB affect host cells to promote intracellular development and evasion of cell-intrinsic host
defenses. Corresponding C. muridarum mutant strains will be employed to elucidate the contributions
of these effectors to pathogenesis in an animal model. A balanced combination of genetic, biochemical,
cell-biology, and animal-based studies are proposed that will define the overall role of these effectors in
establishing and maintaining infectivity that culminates in Chlamydia-mediated disease. Completion of
this work will lead to an enhanced understanding of the molecular mechanisms employed by Chlamydia
to impact host-pathogen interactions igoverning disease.
Status | Active |
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Effective start/end date | 2/6/23 → 1/31/28 |
Funding
- National Institute of Allergy and Infectious Diseases: $574,031.00
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