Date of Award

2009

Degree Type

Thesis

Degree Name

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Miguel Valvano

Second Advisor

Dr. Sung Kim

Third Advisor

Dr. John McCormick

Abstract

Burkholderia cenocepacia is an opportunistic pathogen of cystic fibrosis patients. B. cenocepacia encodes a type VI secretion system (T6SS) under control by the global negative regulator, AtsR. This study demonstrates that while the T6SS is not involved in the characteristic phagosome maturation delay associated with B. cenocepacia, it may play a role in the induction of host cell death. The formation of actin-rich protrusions within infected host cells, previously shown as dependent upon T6SS function, is not a prelude to this cell death, as a mutant deficient in the induction of actin rearrangement still induced cell death. Furthermore, other unknown virulence factors regulated by AtsR may contribute to host cell death, as only loss of T6SS function in conjunction with loss of normal global regulation resulted in reduced host cell death. The host cell death studied appears to not proceed through caspase-3 dependent pathways.

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