Research

The Burkholderia cepacia complex (Bcc) is a problematic group of opportunistic pathogens, particularly in people with cystic fibrosis or chronic granulomatous disease. The Bcc consists of at least nine closely related species that appear to have varying degrees of virulence and ability to transfer between patients. B. cenocepacia is the most common species infecting CF patients in North America and the most frequently associated with severe and often fatal lung infections in CF patients. My research focuses on the determination of both common virulence mechanisms in the Bcc and differential virulence mechanisms that may account for the increased severity of infections by strains of some Bcc species. Our objectives are to understand the mechanisms of Bcc pathogenesis in lung infections with the long term goals of identifying therapeutic strategies or anti-microbial targets.

One global regulatory mechanism used by all Bcc species is quorum sensing (QS) mediated cell-cell communication. QS enables bacteria to regulate gene expression in a way that is advantageous to their cell numbers in a particular environment. We are particularly interested in QS regulated genes expressed during chronic and acute lung infections. Several molecular and bioinformatics techniques are being used to determine the QS regulatory network in B. cenocepacia and B. vietnamiensis.

We are particularly interested in virulence factors that enable some Bcc species able to survive or persist in the presence of host defense mechanisms or to cause more severe lung damage. The zinc metalloproteases ZmpA and ZmpB are two functionally similar but antigenically distinct enzymes that degrade substrates involved in tissue integrity or host defense. Factors that influence colony morphology also result in altered biofilm formation and virulence in B. cenocepacia. The genes involved in this phenotypic variation and their role in pathogenesis are currently being identified and characterized. These studies will help us to understand the differential virulence of the Bcc and why some species have a greater capacity to cause disease in a variety of hosts.