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K-State Today Student Edition

February 8, 2018



Stephanie Shames to present Biochemistry and Molecular Biophysics Seminar today

By Melinda Bainter

Stephanie Shames, Division of Biology, will present "Elucidating the contribution of Legionella pneumophila effector proteins to pathogenesis and host defense" as the first event in the Biochemistry and Molecular Biophysics Seminar series at 4 p.m. Thursday, Feb. 8, in 13 Leasure Hall.

Intracellular bacterial pathogens such as Legionella pneumophila cause disease by using specialized secretion systems to deliver bacterial effector proteins into a host cell to manipulate biological pathways. A single strain of L. pneumophila encodes a repertoire of more than 300 different effector proteins, which are delivered into host cells by the Dot/Icm type IV secretion system. Due to the large number of effector proteins, identifying their contribution to disease has proven to be challenging. We used insertion sequencing — INSeq — to reveal the contribution of effector genes to L. pneumophila virulence. The replication of hundreds of targeted effector mutants was measured in parallel in both a mouse model of Legionnaires’ disease, host cells cultured ex vivo, and a natural amoeba host. We uncovered phenotypes resulting from loss-of-function mutations in several effector genes in the mouse lung and in cultured host cells. Phenotypes of two effectors identified in this screen, LegC4 and Lpg2505, were validated, which demonstrated the robustness of the screen. Our current work is geared toward understanding the role of these effectors in Legionella pathogenesis and host defense.