Chapter 49 : Defining the Translocation Pathway of the Legionella pneumophila Type IV Secretion System

Abstract:

The ability of Legionella pneumophila to cause disease is primarily due to its ability to survive inside alveolar macrophages, immune cells capable of destroying most bacteria. The Dot/Icm proteins make up a type IVB secretion system that is required for delivery of multiple protein substrates into the host cell cytoplasm, where they are believed to alter the endocytic pathway and allow the bacterial phagosome to avoid fusion with lysosomal markers. Type IV secretion systems (T4SSs) are used by many pathogens to deliver substrates to host cells, including Helicobacter pylori, Bordetella pertussis, and Brucella abortus. The secretion systems used by these pathogens are ancestrally related to plasmid transfer systems and are thus referred to as adapted conjugation systems. Our goal is to characterize the molecular details of how the Dot/Icm secretion complex assembles and functions to export substrates. The approaches to understanding these processes are based on techniques that have proven successful in characterizing the canonical T4SS, the VirB/D4 system from the plant pathogen Agrobacterium tumefaciens. To identify functional subcomplexes of the Dot/Icm T4SS, researchers are currently examining protein interactions between Dot/Icm components. One approach researchers are taking to accomplish this is to determine effects on protein stability caused by deletions of other dot/icm genes. This approach is based on the fact that proteins that interact in a complex often require their interaction partners for stability.