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The Burkholderia Type VI Secretion System 5: Composition, Regulation and Role in Virulence
Jan Lennings1, T Eoin West2, Sandra Schwarz1
1Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
Abstract:
The soil saprophyte and Tier I select agent Burkholderia pseudomallei can cause rapidly fatal infections in humans and animals. The capability of switching to an intracellular life cycle during infection appears to be a decisive trait of B. pseudomallei for causing disease. B. pseudomallei harbors multiple type VI secretion systems (T6SSs) orthologs of which are present in the surrogate organism Burkholderia thailandensis. Upon host cell entry and vacuolar escape into the cytoplasm, B. pseudomallei and B. thailandensis manipulate host cells by utilizing the T6SS-5 (also termed T6SS1) to form multinucleated giant cells for intercellular spread. Disruption of the T6SS-5 in B. thailandensis causes a drastic attenuation of virulence in wildtype but not in mice lacking the central innate immune adapter protein MyD88. This result suggests that the T6SS-5 is deployed by the bacteria to overcome innate immune responses. However, important questions in this field remain unsolved including the mechanism underlying T6SS-5 activity and its physiological role during infection. In this review, we summarize the current knowledge on the components and regulation of the T6SS-5 as well as its role in virulence in mammalian hosts.
Insights
Burkholderia pseudomallei uses Type VI Secretion System 5 (T6SS-5) to cause fatal infections by manipulating host cells and evading immune responses. This review details T6SS-5
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- * Burkholderia pseudomallei* is a soil bacterium and select agent causing severe infections.
- * B. pseudomallei*'s intracellular lifestyle is key to its virulence.
- * Type VI Secretion Systems (T6SSs)* are crucial for bacterial-host interactions.
Purpose of the Study:
- To review current knowledge on *Burkholderia*'s T6SS-5.
- To elucidate the mechanism and role of T6SS-5 in virulence.
- To understand how T6SS-5 aids bacteria in overcoming host immunity.
Main Methods:
- Comparative analysis of T6SS orthologs in *B. pseudomallei* and *B. thailandensis*.
- Investigation of T6SS-5 function in host cell manipulation (e.g., multinucleated giant cell formation).
- Assessment of T6SS-5's role in virulence using mouse models with varying innate immunity (MyD88-dependent pathways).
Main Results:
- *B. pseudomallei* and *B. thailandensis* utilize T6SS-5 to manipulate host cells post-entry.
- T6SS-5 facilitates intercellular spread by forming multinucleated giant cells.
- T6SS-5 disruption attenuates virulence in wildtype mice but not in MyD88-deficient mice, indicating a role in overcoming innate immunity.
Conclusions:
- T6SS-5 is a critical virulence factor for *Burkholderia* species.
- The T6SS-5 likely functions to suppress host innate immune responses.
- Further research is needed to fully understand T6SS-5's mechanism and physiological significance during infection.
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