Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.

Pseudomonas aeruginosa is a common environmental bacterium that is also a significant opportunistic pathogen, particularly of the human lung. We must understand how P. aeruginosa responds to the lung environment in order to identify the regulatory changes that bacteria use to establish and maintain...

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Autores principales:	Annette E LaBauve, Matthew J Wargo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6bffa58242fb46aa9c19b5c16287b981
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spelling	oai:doaj.org-article:6bffa58242fb46aa9c19b5c16287b9812021-11-18T06:07:04ZDetection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.1553-73661553-737410.1371/journal.ppat.1003889https://doaj.org/article/6bffa58242fb46aa9c19b5c16287b9812014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465209/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Pseudomonas aeruginosa is a common environmental bacterium that is also a significant opportunistic pathogen, particularly of the human lung. We must understand how P. aeruginosa responds to the lung environment in order to identify the regulatory changes that bacteria use to establish and maintain infections. The P. aeruginosa response to pulmonary surfactant was used as a model to identify transcripts likely induced during lung infection. The most highly induced transcript in pulmonary surfactant, PA5325 (sphA), is regulated by an AraC-family transcription factor, PA5324 (SphR). We found that sphA was specifically induced by sphingosine in an SphR-dependent manner, and also via metabolism of sphingomyelin, ceramide, or sphingoshine-1-phosphate to sphingosine. These sphingolipids not only play a structural role in lipid membranes, but some are also intracellular and intercellular signaling molecules important in normal eukaryotic cell functions as well as orchestrating immune responses. The members of the SphR transcriptome were identified by microarray analyses, and DNA binding assays showed specific interaction of these promoters with SphR, which enabled us to determine the consensus SphR binding site. SphR binding to DNA was modified by sphingosine and we used labeled sphingosine to demonstrate direct binding of sphingosine by SphR. Deletion of sphR resulted in reduced bacterial survival during mouse lung infection. In vitro experiments show that deletion of sphR increases sensitivity to the antimicrobial effects of sphingosine which could, in part, explain the in vivo phenotype. This is the first identification of a sphingosine-responsive transcription factor in bacteria. We predict that SphR transcriptional regulation may be important in response to many sites of infection in eukaryotes and the presence of homologous transcription factors in other pathogens suggests that sphingosine detection is not limited to P. aeruginosa.Annette E LaBauveMatthew J WargoPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 1, p e1003889 (2014)
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 Annette E LaBauve Matthew J Wargo Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
description	Pseudomonas aeruginosa is a common environmental bacterium that is also a significant opportunistic pathogen, particularly of the human lung. We must understand how P. aeruginosa responds to the lung environment in order to identify the regulatory changes that bacteria use to establish and maintain infections. The P. aeruginosa response to pulmonary surfactant was used as a model to identify transcripts likely induced during lung infection. The most highly induced transcript in pulmonary surfactant, PA5325 (sphA), is regulated by an AraC-family transcription factor, PA5324 (SphR). We found that sphA was specifically induced by sphingosine in an SphR-dependent manner, and also via metabolism of sphingomyelin, ceramide, or sphingoshine-1-phosphate to sphingosine. These sphingolipids not only play a structural role in lipid membranes, but some are also intracellular and intercellular signaling molecules important in normal eukaryotic cell functions as well as orchestrating immune responses. The members of the SphR transcriptome were identified by microarray analyses, and DNA binding assays showed specific interaction of these promoters with SphR, which enabled us to determine the consensus SphR binding site. SphR binding to DNA was modified by sphingosine and we used labeled sphingosine to demonstrate direct binding of sphingosine by SphR. Deletion of sphR resulted in reduced bacterial survival during mouse lung infection. In vitro experiments show that deletion of sphR increases sensitivity to the antimicrobial effects of sphingosine which could, in part, explain the in vivo phenotype. This is the first identification of a sphingosine-responsive transcription factor in bacteria. We predict that SphR transcriptional regulation may be important in response to many sites of infection in eukaryotes and the presence of homologous transcription factors in other pathogens suggests that sphingosine detection is not limited to P. aeruginosa.
format	article
author	Annette E LaBauve Matthew J Wargo
author_facet	Annette E LaBauve Matthew J Wargo
author_sort	Annette E LaBauve
title	Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
title_short	Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
title_full	Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
title_fullStr	Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
title_full_unstemmed	Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
title_sort	detection of host-derived sphingosine by pseudomonas aeruginosa is important for survival in the murine lung.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/6bffa58242fb46aa9c19b5c16287b981
work_keys_str_mv	AT annetteelabauve detectionofhostderivedsphingosinebypseudomonasaeruginosaisimportantforsurvivalinthemurinelung AT matthewjwargo detectionofhostderivedsphingosinebypseudomonasaeruginosaisimportantforsurvivalinthemurinelung
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Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.

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