The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner

ABSTRACT The opportunistic pathogen Acinetobacter baumannii is able to persist in the environment and is often multidrug resistant (MDR), causing difficulties in the treatment of infections. Here, we show that the two-component system AdeRS, which regulates the production of the AdeABC multidrug res...

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Autores principales:	Grace E. Richmond, Laura P. Evans, Michele J. Anderson, Matthew E. Wand, Laura C. Bonney, Alasdair Ivens, Kim Lee Chua, Mark A. Webber, J. Mark Sutton, Marnie L. Peterson, Laura J. V. Piddock
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bc0be438a103424e942216a1e120992e
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spelling	oai:doaj.org-article:bc0be438a103424e942216a1e120992e2021-11-15T15:41:41ZThe <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner10.1128/mBio.00430-162150-7511https://doaj.org/article/bc0be438a103424e942216a1e120992e2016-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00430-16https://doaj.org/toc/2150-7511ABSTRACT The opportunistic pathogen Acinetobacter baumannii is able to persist in the environment and is often multidrug resistant (MDR), causing difficulties in the treatment of infections. Here, we show that the two-component system AdeRS, which regulates the production of the AdeABC multidrug resistance efflux pump, is required for the formation of a protective biofilm in an ex vivo porcine mucosal model, which mimics a natural infection of the human epithelium. Interestingly, deletion of adeB impacted only on the ability of strain AYE to form a biofilm on plastic and only on the virulence of strain Singapore 1 for Galleria mellonella. RNA-Seq revealed that loss of AdeRS or AdeB significantly altered the transcriptional landscape, resulting in the changed expression of many genes, notably those associated with antimicrobial resistance and virulence interactions. For example, A. baumannii lacking AdeRS displayed decreased expression of adeABC, pil genes, com genes, and a pgaC-like gene, whereas loss of AdeB resulted in increased expression of pil and com genes and decreased expression of ferric acinetobactin transport system genes. These data define the scope of AdeRS-mediated regulation, show that changes in the production of AdeABC mediate important phenotypes controlled by AdeRS, and suggest that AdeABC is a viable target for antimicrobial drug and antibiofilm discovery. IMPORTANCE Acinetobacter baumannii is a nosocomial pathogen and is an increasing problem in hospitals worldwide. This organism is often multidrug resistant, can persist in the environment, and forms a biofilm on environmental surfaces and wounds. Overproduction of efflux pumps can allow specific toxic compounds to be pumped out of the cell and can lead to multidrug resistance. This study demonstrates the role of the A. baumannii efflux pump AdeB, and its regulator AdeRS, in multidrug resistance, epithelial cell killing, and biofilm formation. Deletion of the genes encoding these systems led to increased susceptibility to antibiotics, decreased biofilm formation on biotic and abiotic surfaces, and decreased virulence. Our data suggest that inhibition of AdeB could prevent biofilm formation or colonization in patients by A. baumannii and provides a good target for drug discovery.Grace E. RichmondLaura P. EvansMichele J. AndersonMatthew E. WandLaura C. BonneyAlasdair IvensKim Lee ChuaMark A. WebberJ. Mark SuttonMarnie L. PetersonLaura J. V. PiddockAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 2 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Grace E. Richmond Laura P. Evans Michele J. Anderson Matthew E. Wand Laura C. Bonney Alasdair Ivens Kim Lee Chua Mark A. Webber J. Mark Sutton Marnie L. Peterson Laura J. V. Piddock The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner
description	ABSTRACT The opportunistic pathogen Acinetobacter baumannii is able to persist in the environment and is often multidrug resistant (MDR), causing difficulties in the treatment of infections. Here, we show that the two-component system AdeRS, which regulates the production of the AdeABC multidrug resistance efflux pump, is required for the formation of a protective biofilm in an ex vivo porcine mucosal model, which mimics a natural infection of the human epithelium. Interestingly, deletion of adeB impacted only on the ability of strain AYE to form a biofilm on plastic and only on the virulence of strain Singapore 1 for Galleria mellonella. RNA-Seq revealed that loss of AdeRS or AdeB significantly altered the transcriptional landscape, resulting in the changed expression of many genes, notably those associated with antimicrobial resistance and virulence interactions. For example, A. baumannii lacking AdeRS displayed decreased expression of adeABC, pil genes, com genes, and a pgaC-like gene, whereas loss of AdeB resulted in increased expression of pil and com genes and decreased expression of ferric acinetobactin transport system genes. These data define the scope of AdeRS-mediated regulation, show that changes in the production of AdeABC mediate important phenotypes controlled by AdeRS, and suggest that AdeABC is a viable target for antimicrobial drug and antibiofilm discovery. IMPORTANCE Acinetobacter baumannii is a nosocomial pathogen and is an increasing problem in hospitals worldwide. This organism is often multidrug resistant, can persist in the environment, and forms a biofilm on environmental surfaces and wounds. Overproduction of efflux pumps can allow specific toxic compounds to be pumped out of the cell and can lead to multidrug resistance. This study demonstrates the role of the A. baumannii efflux pump AdeB, and its regulator AdeRS, in multidrug resistance, epithelial cell killing, and biofilm formation. Deletion of the genes encoding these systems led to increased susceptibility to antibiotics, decreased biofilm formation on biotic and abiotic surfaces, and decreased virulence. Our data suggest that inhibition of AdeB could prevent biofilm formation or colonization in patients by A. baumannii and provides a good target for drug discovery.
format	article
author	Grace E. Richmond Laura P. Evans Michele J. Anderson Matthew E. Wand Laura C. Bonney Alasdair Ivens Kim Lee Chua Mark A. Webber J. Mark Sutton Marnie L. Peterson Laura J. V. Piddock
author_facet	Grace E. Richmond Laura P. Evans Michele J. Anderson Matthew E. Wand Laura C. Bonney Alasdair Ivens Kim Lee Chua Mark A. Webber J. Mark Sutton Marnie L. Peterson Laura J. V. Piddock
author_sort	Grace E. Richmond
title	The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner
title_short	The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner
title_full	The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner
title_fullStr	The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner
title_full_unstemmed	The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner
title_sort	<named-content content-type="genus-species">acinetobacter baumannii</named-content> two-component system aders regulates genes required for multidrug efflux, biofilm formation, and virulence in a strain-specific manner
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/bc0be438a103424e942216a1e120992e
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The <named-content content-type="genus-species">Acinetobacter baumannii</named-content> Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner

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