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Published on: June 10, 2020
Chlamydia pneumoniae facilitates its development by recruiting PI4P to inclusion bodies via the Cpn0308-ACBD3-PI4KB
Xiaonan Feng1, Tian'ai Cao1, Xiaohui Jia1
1Key Laboratory of Clinical Laboratory Diagnostics, Institute of Pathogenic Biology and Immunology, Hebei North University, Zhangjiakou, China.
Abstract:
Chlamydia pneumoniae (Cpn) is an obligate intracellular parasitic pathogen that replicates inside a membrane-bound vacuole termed the inclusion. This compartment is modified by chlamydial inclusion membrane proteins (Incs), which interact with host proteins to facilitate chlamydial development and pathogenicity. Among these, Cpn0308 localizes specifically to the inclusion membrane. Our previous study demonstrated that exogenously expressed Cpn0308 can interact with host protein ACBD3; here, we demonstrate this interaction during actual Cpn infection using endogenous proteins. This interplay proved critical for Cpn development, as ACBD3 knockout in HeLa cells led to significantly smaller inclusions, delayed transition from elementary bodies (EBs) to reticulate bodies (RBs), and reduced bacterial copy numbers. Mechanistically, the Cpn0308-ACBD3 interaction facilitates the recruitment of Phosphatidylinositol 4-kinase 3β (PI4KB) to the inclusion vicinity. This recruitment enhances the production and localization of Phosphatidylinositol 4-phosphate (PI4P) within Cpn-infected HeLa cells. Conversely, PI4KB and PI4P levels were markedly diminished in Cpn-infected ACBD3-knockout cells, whereas their expression remained unchanged in uninfected knockout cells. Furthermore, pharmacological inhibition of PI4KB with PIK93 impaired PI4P synthesis and suppressed Cpn replication. In conclusion, we propose a mechanism wherein the Cpn inclusion membrane protein Cpn0308 engages host ACBD3 to recruit PI4KB around the inclusion, which subsequently catalyzes PI4P production, thereby promoting the development and progression of C. pneumoniae infection.
Insights
Chlamydia pneumoniae uses its Cpn0308 protein to interact with host ACBD3, recruiting PI4KB to produce PI4P. This process is essential for chlamydial development and infection progression.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Chlamydia pneumoniae (Cpn) is an intracellular pathogen that modifies host cell vacuoles (inclusions) using inclusion membrane proteins (Incs).
- Cpn0308 is a Cpn Inc that localizes to the inclusion membrane and interacts with host proteins.
Purpose of the Study:
- To investigate the interaction between Cpn0308 and host protein ACBD3 during Cpn infection.
- To elucidate the mechanism by which this interaction affects Cpn development and pathogenicity.
Main Methods:
- Utilized ACBD3 knockout HeLa cells to assess Cpn development.
- Employed endogenous protein analysis to confirm Cpn0308-ACBD3 interaction during infection.
- Investigated the role of Phosphatidylinositol 4-kinase 3β (PI4KB) and Phosphatidylinositol 4-phosphate (PI4P) in the Cpn0308-ACBD3 pathway.
- Used pharmacological inhibition of PI4KB to evaluate its impact on Cpn replication.
Main Results:
- ACBD3 knockout significantly reduced inclusion size, delayed pathogen development (EB to RB transition), and decreased bacterial load.
- The Cpn0308-ACBD3 interaction facilitates PI4KB recruitment, enhancing PI4P production at the inclusion.
- PI4KB inhibition suppressed PI4P synthesis and inhibited Cpn replication.
Conclusions:
- Cpn0308 interacts with host ACBD3 to recruit PI4KB, promoting PI4P synthesis.
- This PI4P production is crucial for the development and progression of C. pneumoniae infection.
- The Cpn0308-ACBD3-PI4KB-PI4P axis represents a key host-pathogen interplay for Cpn survival.
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