Type VI secretion is a major virulence determinant in Burkholderia mallei

Mark A Schell1, Ricky L Ulrich, Wilson J Ribot

  • 1Department of Microbiology, University of Georgia, Athens, GA 30602, USA.

Insights

The VirAG system in Burkholderia mallei regulates virulence, with type VI secretion (T6S) genes being crucial. Overexpression of VirAG activates T6S genes, and mutations in these genes render the bacteria avirulent in hamsters.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Burkholderia mallei is a significant pathogen and biothreat agent.
  • The VirAG two-component system is essential for B. mallei virulence, but its regulated targets remain unidentified.

Purpose of the Study:

  • To identify virulence genes regulated by the VirAG system in Burkholderia mallei.
  • To elucidate the role of VirAG-controlled factors in bacterial virulence.

Main Methods:

  • Gene expression profiling using microarrays to assess transcriptional changes upon VirAG overexpression.
  • Genetic manipulation to create mutations in identified virulence gene clusters.
  • Biochemical assays including SDS-PAGE and mass spectrometry for protein secretion analysis.
  • Animal models (hamsters) to assess bacterial virulence and survival.

Main Results:

  • Overexpression of virAG led to the transcriptional activation of approximately 60 genes, including those involved in capsule production, actin-based motility, and type VI secretion (T6S).
  • Actin polymerization, while dependent on virAG and novel genes (bimB, bimC, bimE), was found to be dispensable for hamster virulence.
  • Genes encoding a T6S system were significantly upregulated (up to 30-fold), and mutations in this cluster resulted in complete avirulence in hamsters.
  • The T6S system secreted the Hcp-family protein BMAA0742, which was recognized by antibodies from infected hosts, indicating its in vivo production.

Conclusions:

  • The VirAG regulatory system controls key virulence factors in Burkholderia mallei, notably the type VI secretion system.
  • The type VI secretion system and its secreted effector BMAA0742 are critical for B. mallei virulence in a hamster model.
  • Actin motility is not essential for virulence, highlighting the primary role of T6S in host-pathogen interactions.

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