File(s) stored somewhere else
Please note: Linked content is NOT stored on La Trobe and we can't guarantee its availability, quality, security or accept any liability.
The Burkholderia pseudomallei type III secretion system and BopA are required for evasion of LC3-associated phagocytosis
journal contributionposted on 2021-02-16, 06:00 authored by L Gong, Meabh CullinaneMeabh Cullinane, P Treerat, G Ramm, M Prescott, B Adler, JD Boyce, RJ Devenish
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. © 2011 Gong et al.
Pagination11p. (p. 1-11)
PublisherPublic Library of Science
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
Science & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsGROUP-A STREPTOCOCCUSINTRACELLULAR SHIGELLAINFECTED MACROPHAGESAUTOPHAGIC PATHWAYMELIOIDOSISSURVIVALESCAPECELLSHOSTVIRULENCECell LineIntracellular SpacePhagosomesVacuolesCytosolAnimalsMiceBurkholderia pseudomalleiBacterial ProteinsMicrotubule-Associated ProteinsPhagocytosisGene Expression Regulation, BacterialProtein TransportMutationAutophagyLysosome-Associated Membrane GlycoproteinsImmune EvasionGeneral Science & Technology