The Cluster 1 Type VI Secretion System Is a Major Virulence Determinant in Burkholderia pseudomallei
- 1 April 2011
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 79 (4), 1512-1525
- https://doi.org/10.1128/iai.01218-10
Abstract
The Burkholderia pseudomallei K96243 genome encodes six type VI secretion systems (T6SSs), but little is known about the role of these systems in the biology of B. pseudomallei . In this study, we purified recombinant Hcp proteins from each T6SS and tested them as vaccine candidates in the BALB/c mouse model of melioidosis. Recombinant Hcp2 protected 80% of mice against a lethal challenge with K96243 , while recombinant Hcp1, Hcp3, and Hcp6 protected 50% of mice against challenge. Hcp6 was the only Hcp constitutively produced by B. pseudomallei in vitro ; however, it was not exported to the extracellular milieu. Hcp1, on the other hand, was produced and exported in vitro when the VirAG two-component regulatory system was overexpressed in trans . We also constructed six hcp deletion mutants ( Δhcp1 through Δhcp6 ) and tested them for virulence in the Syrian hamster model of infection. The 50% lethal doses (LD 50 s) for the Δhcp2 through Δhcp6 mutants were indistinguishable from K96243 (10 3 bacteria. The hcp1 deletion mutant also exhibited a growth defect in RAW 264.7 macrophages and was unable to form multinucleated giant cells in this cell line. Unlike K96243 , the Δhcp1 mutant was only weakly cytotoxic to RAW 264.7 macrophages 18 h after infection. The results suggest that the cluster 1 T6SS is essential for virulence and plays an important role in the intracellular lifestyle of B. pseudomallei .Keywords
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