Type IVb protein secretion
Legionella pneumophila is a facultative pathogen that preys upon alveolar macrophages by subverting the endosome-lysosome pathway. In the first stage, a Type IVb protein secretion system (T4bSS) assembles at regions of contact between the bacterium and the target cell. This Dot/Icm apparatus translocates protein effectors into the macrophage cytoplasm. This helps transform the phagosome carrying Legionella into an ER-like compartment, which allows Legionella to grow within the cell. Finally, the macrophage is lysed and new bacteria emerge into the lung cavity. Repeated cycles lead to inflammation and a deadly pneumonia known as Legionnaires’ disease.
Our long term goal is to create a detailed molecular model of the T4bSS, which is comprised of ~27 Dot/Icm gene products. As a first step, we are evaluating the role of IcmR-IcmQ, which may be involved in assembly or stabilization of the translocase. We are also studying a putative DotA channel and the IcmS-IcmW transport receptor.