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Type III Secretion in the Melioidosis Pathogen Burkholderia pseudomallei
Charles W Vander Broek1, Joanne M Stevens1
1The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of EdinburghMidlothian, United Kingdom.
Abstract:
Burkholderia pseudomallei is a Gram-negative intracellular pathogen and the causative agent of melioidosis, a severe disease of both humans and animals. Melioidosis is an emerging disease which is predicted to be vastly under-reported. Type III Secretion Systems (T3SSs) are critical virulence factors in Gram negative pathogens of plants and animals. The genome of B. pseudomallei encodes three T3SSs. T3SS-1 and -2, of which little is known, are homologous to Hrp2 secretion systems of the plant pathogens Ralstonia and Xanthomonas. T3SS-3 is better characterized and is homologous to the Inv/Mxi-Spa secretion systems of Salmonella spp. and Shigella flexneri, respectively. Upon entry into the host cell, B. pseudomallei requires T3SS-3 for efficient escape from the endosome. T3SS-3 is also required for full virulence in both hamster and murine models of infection. The regulatory cascade which controls T3SS-3 expression and the secretome of T3SS-3 have been described, as well as the effect of mutations of some of the structural proteins. Yet only a few effector proteins have been functionally characterized to date and very little work has been carried out to understand the hierarchy of assembly, secretion and temporal regulation of T3SS-3. This review aims to frame current knowledge of B. pseudomallei T3SSs in the context of other well characterized model T3SSs, particularly those of Salmonella and Shigella.
Insights
Burkholderia pseudomallei uses three Type III Secretion Systems (T3SSs) for virulence. This review focuses on T3SS-3, crucial for bacterial escape and disease progression, comparing it to Salmonella and Shigella systems.
Area of Science:
- Microbiology
- Pathogenesis
- Bacterial Secretion Systems
Background:
- Burkholderia pseudomallei is a Gram-negative intracellular pathogen causing melioidosis, a severe and under-reported emerging disease in humans and animals.
- Type III Secretion Systems (T3SSs) are critical virulence factors in Gram-negative pathogens.
- B. pseudomallei possesses three T3SSs, with T3SS-3 being homologous to Salmonella and Shigella systems and essential for virulence.
Purpose of the Study:
- To review and frame current knowledge of B. pseudomallei T3SSs.
- To contextualize B. pseudomallei T3SSs, particularly T3SS-3, with well-characterized model T3SSs from Salmonella and Shigella.
- To highlight gaps in understanding T3SS-3 assembly, secretion, and regulation.
Main Methods:
- Literature review and synthesis of existing research on B. pseudomallei T3SSs.
- Comparative analysis of T3SS-3 with homologous systems in Salmonella and Shigella.
- Discussion of known regulatory cascades, secretomes, and effector proteins of T3SS-3.
Main Results:
- T3SS-3 is essential for B. pseudomallei's endosomal escape within host cells.
- T3SS-3 contributes significantly to virulence in both hamster and murine infection models.
- While T3SS-3 regulation and secretome are partially described, few effector proteins are functionally characterized.
Conclusions:
- T3SS-3 is a key virulence determinant in B. pseudomallei, playing a vital role in host cell manipulation.
- Further research is needed to elucidate the assembly, secretion hierarchy, and temporal regulation of T3SS-3.
- Comparative studies with Salmonella and Shigella T3SSs provide valuable insights for understanding B. pseudomallei pathogenesis.
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