Date of Award
2010
Degree Type
Thesis
Degree Name
Master of Science
Program
Microbiology and Immunology
Supervisor
Dr. Miguel Valvano
Second Advisor
Dr. Sung Kim
Third Advisor
Dr. Paul Walton
Abstract
Burkholderia cenocepacia is a Gram-negative opportunistic pathogen that primarily infects cystic fibrosis patients. Recently a B. cenocepacia Type VI Secretion System (T6SS) was demonstrated to be able to induce actin rearrangements in infected macrophages. Initial experiments confirmed that contact between the host cell and B. cenocepacia is required to induce this phenotype. Live imaging of infected macrophages revealed that the mechanism behind these cellular morphology changes was associated with defects in cell retraction. Activation of the RhoGTPase Racl was inhibited in a T6SS dependent manner and transfection of macrophages with a plasmid encoding a constitutively active Racl reduced their susceptibility to these actin rearrangements in comparison to cells transfected with wild-type Racl. Functional analysis of the infected macrophages determined that migration was increased by the T6SS while FcγR phagocytosis was inhibited. A better understanding of the T6SS will provide important insight into B. cenocepacia infection.
Recommended Citation
Skeldon, Alexander M.T., "The Burkholderia cenocepacia T6SS inhibits the RhoGTPase Racl and affects the function of infected macrophages" (2010). Digitized Theses. 4764.
https://ir.lib.uwo.ca/digitizedtheses/4764