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Cited by 175Burkholderia infections and melioidosisBacillus and Francisella bacterial researchBacterial Infections and Vaccines

The Burkholderia pseudomallei Type III Secretion System and BopA Are Required for Evasion of LC3-Associated Phagocytosis

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Gong, Lan, Cullinane, Meabh, Treerat, Puthayalai, Ramm, Georg, Prescott, Mark, Adler, Ben, Boyce, John D., Devenish, Rodney J.·2011·PLoS ONE
DOI 10.1371/journal.pone.0017852PMC PMC3055895
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Abstract

Burkholderia pseudomallei is the causative agent of melioidosis, a fatal infectious disease endemic in tropical regions worldwide, and especially prevalent in southeast Asia and northern Australia. This intracellular pathogen can escape from phagosomes into the host cytoplasm, where it replicates and infects adjacent cells. We previously demonstrated that, in response to B. pseudomallei infection of macrophage cell line RAW 264.7, a subset of bacteria co-localized with the autophagy marker protein, microtubule-associated protein light chain 3 (LC3), implicating autophagy in host cell defence against infection. Recent reports have suggested that LC3 can be recruited to both phagosomes and autophagosomes, thereby raising questions regarding the identity of the LC3-positive compartments in which invading bacteria reside and the mechanism of the autophagic response to B. pseudomallei infection. Electron microscopy analysis of infected cells demonstrated that the invading bacteria were either free in the cytosol, or sequestered in single-membrane phagosomes rather than double-membrane autophagosomes, suggesting that LC3 is recruited to B. pseudomallei-containing phagosomes. Partial or complete loss of function of type III secretion system cluster 3 (TTSS3) in mutants lacking the BopA (effector) or BipD (translocator) proteins respectively, resulted in delayed or no escape from phagosomes. Consistent with these observations, bopA and bipD mutants both showed a higher level of co-localization with LC3 and the lysosomal marker LAMP1, and impaired survival in RAW264.7 cells, suggesting enhanced killing in phagolysosomes. We conclude that LC3 recruitment to phagosomes stimulates killing of B. pseudomallei trapped in phagosomes. Furthermore, BopA plays an important role in efficient escape of B. pseudomallei from phagosomes.

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  • In Burkholderia pseudomallei infection of GFP-LC3 expressing RAW macrophage cells, intracellular bacteria reside within LC3-positive phagosomes, from which they later escape into the cytosol.

    “In the case of Burkholderia pseudomallei infection of GFP-LC3 expressing RAW macrophage cells, the intracellular bacteria reside within LC3-positive phagosomes [13], from which they later escape into the cytosol.”

    From LC3-Associated Phagocytosis (LAP): Connections with Host Autophagy (2012) · cites this paper as [13]

    The Results section (page unavailable) reports that approximately 5–10% of wild-type bacteria were associated with LC3 at 2 hours and suggests that LC3 is recruited to bacteria-containing phagosomes. Figure 2 says that most wild-type bacteria escape from phagosomes into the cytosol, but the paper does not show that they escape specifically from LC3-positive phagosomes. The claim also omits that LC3 association was observed in only a small subset. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • LC3 can be recruited to single-membrane phagosomes in a process termed LC3-associated phagocytosis (LAP).

    “Recently, it has been demonstrated that LC3 can be recruited to other membranes including single-membrane phagosomes, in a process termed LC3-associated phagocytosis (LAP).”

    From LC3-Associated Phagocytosis (LAP): Connections with Host Autophagy (2012) · cites this paper as [13]

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References 53 · Cited by 175

Research works printed but not linked: 49

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Authors
Gong, L., Cullinane, M., Treerat, P., Ramm, G., Prescott, M., Adler, B., Boyce, J. D., & Devenish, R. J.
Affiliations
  • Australian Research Council (AU)
  • Monash University (AU)
Corresponding author
  • Boyce, John D.
  • Devenish, Rodney J.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-03-11
Volume
6
Issue
3
Pages
e17852
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0017852
PMC
PMC3055895
OpenAlex
W2048656742
Cited by
175
References
53
Citations by year
2026: 8 · 2025: 9 · 2024: 9 · 2023: 9 · 2022: 7 · 2021: 10 · 2020: 9 · 2019: 13 · 2018: 7 · 2017: 19 · 2016: 12 · 2015: 14 · 2014: 20 · 2013: 14 · 2012: 8
FWCI
11.81
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Medical Research Council
  • Australian Research Council
  • National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Epidemiology › Burkholderia infections and melioidosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacillus and Francisella bacterial research
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords
Burkholderia pseudomallei, melioidosis, type III secretion system, BOPA, BiPd, LC3, autophagy, phagosome escape, intracellular bacterial survival, macrophages, bacterial effector proteins, translocators
MeSH terms
Animals, Autophagy, Bacterial Proteins, Cell Line, Cytosol, Microtubule-Associated Proteins, Mutation, Phagocytosis, Phagosomes, Vacuoles, Gene Expression Regulation, Bacterial, Burkholderia pseudomallei, Protein Transport, Intracellular Space, Mice, Lysosomal Membrane Proteins, Lysosomal-Associated Membrane Protein 1, Immune Evasion

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