Rapid nutritional remodeling of the host cell upon attachment of Legionella pneumophila.
Infect Immun
; 82(1): 72-82, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24126522
ABSTRACT
Upon entry of Legionella pneumophila into amoebas and macrophages, host-mediated farnesylation of the AnkB effector enables its anchoring to the Legionella-containing vacuole (LCV) membrane. On the LCV, AnkB triggers docking of K(48)-linked polyubiquitinated proteins that are degraded by the host proteasomes to elevate cellular levels of amino acids needed for intracellular proliferation. Interference with AnkB function triggers L. pneumophila to exhibit a starvation response and differentiate into the nonreplicative phase in response to the basal levels of cellular amino acids that are not sufficient to power intracellular proliferation of L. pneumophila. Therefore, we have determined whether the biological function of AnkB is temporally and spatially triggered upon bacterial attachment to the host cell to circumvent a counterproductive bacterial differentiation into the nonreplicative phase upon bacterial entry. Here, we show that upon attachment of L. pneumophila to human monocyte-derived macrophages (hMDMs), the host farnesylation and ubiquitination machineries are recruited by the Dot/Icm system to the plasma membrane exclusively beneath sites of bacterial attachment. Transcription and injection of ankB is triggered by attached extracellular bacteria followed by rapid farnesylation and anchoring of AnkB to the cytosolic side of the plasma membrane beneath bacterial attachment, where K(48)-linked polyubiquitinated proteins are assembled and degraded by the proteasomes, leading to a rapid rise in the cellular levels of amino acids. Our data represent a novel strategy by an intracellular pathogen that triggers rapid nutritional remodeling of the host cell upon attachment to the plasma membrane, and as a result, a gratuitous surplus of cellular amino acids is generated to support proliferation of the incoming pathogen.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aderência Bacteriana
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Legionella pneumophila
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Anquirinas
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Proteínas Periplásmicas de Ligação
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Interações Hospedeiro-Patógeno
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Aminoácidos
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Macrófagos
Limite:
Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2014
Tipo de documento:
Article