The final gate: bacterial subversion of autophagosome-lysosome fusion as a conserved immune evasion strategy
Issued Date
2025-01-01
Resource Type
ISSN
1040841X
eISSN
15497828
Scopus ID
2-s2.0-105017045922
Pubmed ID
40974603
Journal Title
Critical Reviews in Microbiology
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SCOPUS
Bibliographic Citation
Critical Reviews in Microbiology (2025)
Suggested Citation
Chowdhury I., Siregar T.A.P., Haque M.F., Ponpuak M. The final gate: bacterial subversion of autophagosome-lysosome fusion as a conserved immune evasion strategy. Critical Reviews in Microbiology (2025). doi:10.1080/1040841X.2025.2562930 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112401
Title
The final gate: bacterial subversion of autophagosome-lysosome fusion as a conserved immune evasion strategy
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Author's Affiliation
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Abstract
Autophagy is a vital component of the host cell intracellular defense arsenal, culminating in the fusion of autophagosomes with lysosomes to degrade invading pathogens. While autophagosome formation has been extensively studied, recent insights reveal that the final fusion step constitutes a critical immunological bottleneck that is highly vulnerable to microbial sabotage. In this review, we synthesize evidence from diverse pathogens, including Mycobacterium tuberculosis, Salmonella enterica, Treponema pallidum, Helicobacter pylori, Coxiella burnetii, Yersinia pestis, and Porphyromonas gingivalis, demonstrating that autophagosome-lysosome fusion blockade is not incidental but represents a convergently evolved immune evasion strategy. We dissect three mechanistic strategies employed by these pathogens: disruption of RAB GTPases, interference with the HOPS and SNARE complexes, and inhibition or misregulation of lysosomal biogenesis and positioning. Each strategy targets the fusion machinery with remarkable specificity, often hijacking host regulatory circuits. We further discuss how these insights inform therapeutic interventions aimed at restoring autophagic flux. Fusion arrest emerges as a unifying hallmark of pathogen survival, positioning autophagosome-lysosome fusion as a critical frontier in the host-pathogen conflict. We advocate a paradigm shift from studying autophagy initiation markers to evaluating fusion competence as a functional measure of autophagic immunity.