Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.

Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Typ...

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Autores principales:	Xavier Charpentier, Joëlle E Gabay, Moraima Reyes, Jing W Zhu, Arthur Weiss, Howard A Shuman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c2fb3b75d8864413b3670cb4e066a45a
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spelling	oai:doaj.org-article:c2fb3b75d8864413b3670cb4e066a45a2021-11-25T05:47:48ZChemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.1553-73661553-737410.1371/journal.ppat.1000501https://doaj.org/article/c2fb3b75d8864413b3670cb4e066a45a2009-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19578436/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system cannot be detected until the bacterium encounters a target host cell. We used chemical genetics, a perturbation strategy that utilizes small molecule inhibitors, to determine the mechanisms critical for L. pneumophila Icm/Dot activity. From a collection of more than 2,500 annotated molecules we identified specific inhibitors of effector translocation. We found that L. pneumophila effector translocation in macrophages requires host cell factors known to be involved in phagocytosis such as phosphoinositide 3-kinases, actin and tubulin. Moreover, we found that L. pneumophila phagocytosis and effector translocation also specifically require the receptor protein tyrosine phosphate phosphatases CD45 and CD148. We further show that phagocytosis is required to trigger effector delivery unless intimate contact between the bacteria and the host is artificially generated. In addition, real-time analysis of effector translocation suggests that effector export is rate-limited by phagocytosis. We propose a model in which L. pneumophila utilizes phagocytosis to initiate an intimate contact event required for the translocation of pre-synthesized effector molecules. We discuss the need for host cell participation in the initial step of the infection and its implications in the L. pneumophila lifestyle. Chemical genetic screening provides a novel approach to probe the host cell functions and factors involved in host-pathogen interactions.Xavier CharpentierJoëlle E GabayMoraima ReyesJing W ZhuArthur WeissHoward A ShumanPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 7, p e1000501 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Xavier Charpentier Joëlle E Gabay Moraima Reyes Jing W Zhu Arthur Weiss Howard A Shuman Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.
description	Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system cannot be detected until the bacterium encounters a target host cell. We used chemical genetics, a perturbation strategy that utilizes small molecule inhibitors, to determine the mechanisms critical for L. pneumophila Icm/Dot activity. From a collection of more than 2,500 annotated molecules we identified specific inhibitors of effector translocation. We found that L. pneumophila effector translocation in macrophages requires host cell factors known to be involved in phagocytosis such as phosphoinositide 3-kinases, actin and tubulin. Moreover, we found that L. pneumophila phagocytosis and effector translocation also specifically require the receptor protein tyrosine phosphate phosphatases CD45 and CD148. We further show that phagocytosis is required to trigger effector delivery unless intimate contact between the bacteria and the host is artificially generated. In addition, real-time analysis of effector translocation suggests that effector export is rate-limited by phagocytosis. We propose a model in which L. pneumophila utilizes phagocytosis to initiate an intimate contact event required for the translocation of pre-synthesized effector molecules. We discuss the need for host cell participation in the initial step of the infection and its implications in the L. pneumophila lifestyle. Chemical genetic screening provides a novel approach to probe the host cell functions and factors involved in host-pathogen interactions.
format	article
author	Xavier Charpentier Joëlle E Gabay Moraima Reyes Jing W Zhu Arthur Weiss Howard A Shuman
author_facet	Xavier Charpentier Joëlle E Gabay Moraima Reyes Jing W Zhu Arthur Weiss Howard A Shuman
author_sort	Xavier Charpentier
title	Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.
title_short	Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.
title_full	Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.
title_fullStr	Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.
title_full_unstemmed	Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.
title_sort	chemical genetics reveals bacterial and host cell functions critical for type iv effector translocation by legionella pneumophila.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/c2fb3b75d8864413b3670cb4e066a45a
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_version_	1718414481879465984

Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila.

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