Engledow, Amanda Suzanne (2006-08). Role of type IV secretion systems in trafficking of virulence determinants of Burkholderia cenocepacia. Doctoral Dissertation.
Type IV secretion systems have been identified in several human pathogens including Bordetella pertussis, Helicobacter pylori, and Legionella pneumophila. These systems are responsible for the translocation of virulence proteins and/or DNA, thereby playing an important role in the pathogenesis of infection and plasticity of genomes. Burkholderia cenocepacia is an important opportunistic human pathogen, particularly in persons with cystic fibrosis (CF). Respiratory tract infection by B. cenocepacia in CF patients is often associated with a decline in respiratory function, and can result in acute systemic infection. Burkholderia cenocepacia strain K56-2 is part of the epidemic and clinically problematic ET12 lineage. Two type IV secretion systems have been identified in this strain; one system is plasmid encoded (designated the Ptw type IV secretion system) whereas the other is chromosomally encoded (designated the VirB/D type IV secretion system) and shows homology to the Agrobacterium tumefaciens VirB/D4 type IV secretion system. It was determined that the plasmid encoded Ptw system is a chimeric type IV secretion system composed of VirB/D4-like elements and F-specific subunits. More recently, it was found that this system translocates a protein effector (PtwE1) that is cytotoxic to plant cells. It was also determined that the positively charged C-terminal region of PtwE1 is important for translocation via the Ptw type IV secretion system. Strains of the epidemic B. cenocepacia PHDC lineage contain only a chromosomal VirB/D4-like type IV secretion system (designated BcVirB/D); and a putative effector protein associated with this system has been identified that has C-terminal transport signal and sequences different from the effectors of the Ptw type IV secretion system. It has also been shown that a competing plasmid substrate and a plasmid fertility inhibition factor act to render B. cenocepacia of the PHDC lineage incapable of expressing a plant phenotype. Thus, three type IV secretion systems have been identified in epidemic B. cenocepacia lineages. From two of these, an effector has been identified that has cytotoxic effects on eukaryotic cells, and at least one of these type IV secretion systems is able to translocate DNA substrates.