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Type VI Secretion System Accessory Protein TagAB-5 Promotes Burkholderia pseudomallei Pathogenicity in Human

Sanisa Lohitthai1, Amporn Rungruengkitkun1, Niramol Jitprasutwit2

  • 1Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.

Biomedicines
|November 25, 2023
PubMed

Insights

The type VI secretion system accessory protein TagAB-5 is crucial for Burkholderia pseudomallei pathogenicity in central nervous system (CNS) microglia. Deleting tagAB-5 impairs bacterial replication and cell damage, highlighting microglia as a key niche for CNS melioidosis.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Neuroscience

Background:

  • Central nervous system (CNS) melioidosis, caused by Burkholderia pseudomallei, presents a significant mortality risk.
  • Understanding B. pseudomallei pathogenesis in the CNS is critical for developing effective treatments.
  • The type VI secretion system (T6SS) is a key virulence factor in bacterial infections.

Purpose of the Study:

  • To investigate the role of the T6SS accessory protein TagAB-5 in B. pseudomallei pathogenicity within the CNS.
  • To examine the interaction of B. pseudomallei with human microglial cells (HCM3) as a model for CNS infection.

Main Methods:

  • Construction of a B. pseudomallei tagAB-5 mutant strain using markerless allele replacement.
  • Infection assays using the human microglial cell line HCM3 to assess bacterial pathogenicity.
  • Evaluation of bacterial intracellular replication, multinucleated giant cell formation, and cell damage induction.
  • Measurement of interleukin-8 (IL-8) production in HCM3 cells.
  • Virulence assessment in the Galleria mellonella model.

Main Results:

  • The tagAB-5 mutant showed significantly reduced intracellular replication, multinucleated giant cell formation, and cell damage in HCM3 cells compared to wild-type.
  • Infection with the tagAB-5 mutant resulted in decreased IL-8 production in HCM3 cells, indicating TagAB-5's role in microglia-mediated inflammation.
  • No significant difference in virulence was observed between the mutant and wild-type strains in the Galleria mellonella model.

Conclusions:

  • Microglia serve as an important intracellular niche for B. pseudomallei, particularly in CNS infections.
  • The T6SS accessory protein TagAB-5 is essential for B. pseudomallei pathogenicity in microglia.
  • TagAB-5 contributes to B. pseudomallei's ability to induce inflammation and damage within the CNS environment.
Keywords:
Burkholderia pseudomalleiGalleria mellonellaneuropathogenesistype VI secretion system

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