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PMID: 21743811 Published · epublish English Journal Article

Secrets of a successful pathogen: legionella resistance to progression along the autophagic pathway.

Frontiers in microbiology ·Vol. 2 ·2011-00-00 ·Pages 138

Joshi AD, Swanson MS

Abstract

To proliferate within phagocytes, Legionella pneumophila relies on Type IV secretion to modulate host cellular pathways. Autophagy is an evolutionarily conserved degradative pathway that captures and transfers a variety of microbes to lysosomes. Biogenesis of L. pneumophila-containing vacuoles and autophagosomes share several features, including endoplasmic reticulum (ER)-derived membranes, contributions by the host GTPases Rab1, Arf1 and Sar1, and a final destiny in lysosomes. We discuss morphological, molecular genetic, and immunological data that support the model that, although A/J mouse macrophages efficiently engulf L. pneumophila within autophagosomal membranes, the Type IV effector proteins DrrA/SidM, LidA, and RalF prolong association with the ER. By inhibiting immediately delivery to lysosomes, the bacteria persist in immature autophagosomal vacuoles for a period sufficient to differentiate into an acid-resistant, replicative form. Subsequent secretion of the Type IV effector LepB releases the block to autophagosome maturation, and the adapted progeny continue to replicate within autophagolysosomes. Accordingly, L. pneumophila can be exploited as a genetic tool to analyze the recruitment and function of the macrophage autophagy pathway.

Keywords
Legionella pneumophila Rab conversion Type IV secretion system autophagy vacuole maturation
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Joshi Amrita D
Department of Microbiology and Immunology, University of Michigan Medical School Ann Arbor, MI, USA.
Swanson Michele S
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Article Info
Journal
Frontiers in microbiology
Abbr.
Front Microbiol
ISSN
1664-302X
Published
2011-00-00
Epub
2011-00-28
Pages
138
Language
English
Region
Switzerland
NLM ID
101548977
PMCID
PMC3127087
Grants
NIAID NIH HHS · R56 AI076300 · United States
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