Analysis of Type VI Secretion in Burkholderia pseudomallei

PI: Dr. Joseph Mougous

Department of Microbiology
University of Washington, Seattle, WA

Pathogenic bacteria make extensive use of secreted proteins in order to colonize and persist in their hosts. Recently, a type VI protein secretion system (T6SS) of Burkholderia pseudomallei, the causative agent of melioidosis, was shown to be a major virulence determinant of the organism. The mechanistic basis for the role of T6S in B. pseudomallei virulence is not known. Interestingly, the genome of this organism encodes five additional T6SSs that have not been investigated; accounting for greater than 2% of its genomic coding capacity. Given the widespread relevance of this protein translocation system in bacteria-host interactions, it is likely that these additional T6SSs also play critical roles for this organism.

The focus of this research is to characterize several aspects of the T6SSs of B. pseudomallei. Studies include measurements of the involvement of each system in virulence and host interactions, identification of regulatory pathways of the systems, and investigation of the role of a predicted post-translational control mechanism. In addition, quantitative mass spectrometric approach is being used to identify novel T6S substrates. The phenotypic profile of each secretion system, the identification of regulators, and the identities of T6S substrates, provides a solid foundation for future investigation of T6S in this organism.