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The role of Legionella Dot/Icm effectors in host-pathogen interactions

thesis
posted on 2017-02-16, 04:17 authored by Lee, Woon Ching
Legionella pneumophila is a facultative intracellular aerobe that causes legionellosis. Among the serogroups, L. pneumophila serogroup 1 is responsible for most of the reported cases of legionellosis. Once internalized by alveolar macrophages in humans, the bacterium will replicate and escalate its intracellular infection resulting in the disease. To survive and replicate in host cells, L. pneumophila relies on effector proteins translocated into host cells via the Legionella Dot/Icm type IV secretion system. Due to the similarities of many Dot/Icm effectors with eukaryotic proteins, the host cell signalling pathways are often the target of these effectors. Using RFLP-hybridization, the polymorphism and distribution of the sidB family effector genes (sidB, sdbA, sdbB and sdbC) were investigated in Legionella spp. All L. pneumophila serogroup 1 and most of serogroup 2-14 showed the presence of all four sidB family effector genes. Interestingly, sdbB was absent in all non-pneumophila Legionella isolates, suggesting that this gene may contribute to the virulence of L. pneumophila. Although the molecular function of the SidB family effectors is unknown, their sequences suggest that they may share similarity with eukaryotic lipases. Localization studies using GFP-tagged SidB effectors revealed that these proteins displayed a distinct and similar vesicular staining pattern within the host cells. When expressed ectopically in HeLa cells, both SidB-GFP and SdbB-GFP on their own led to the disintegration of the cis- and trans-compartments of the Golgi apparatus. Co-localization studies showed that both SidB and SdbB co-localized in the cytosol of HeLa cells surrounding the nucleus. Similarly, both SdbA and SdbC were co-localized in the cytosol of HeLa cells. Interestingly, loss of either one of the sidB genes results in a deficient uptake of the bacteria by mammalian cells, suggesting a potential role for SidB family effectors in promoting entry of L. pneumophila into host cells.

History

Campus location

Australia

Principal supervisor

Sek Chuen Chow

Year of Award

2014

Department, School or Centre

School of Sciences (Monash University Malaysia)

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Science

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