Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>

ABSTRACT Acinetobacter baumannii is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Eun-Jeong Yoon, Yassine Nait Chabane, Sylvie Goussard, Erik Snesrud, Patrice Courvalin, Emmanuelle Dé, Catherine Grillot-Courvalin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/087e00b022194642a80116adf350c7b8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:087e00b022194642a80116adf350c7b8
record_format	dspace
spelling	oai:doaj.org-article:087e00b022194642a80116adf350c7b82021-11-15T15:41:34ZContribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>10.1128/mBio.00309-152150-7511https://doaj.org/article/087e00b022194642a80116adf350c7b82015-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00309-15https://doaj.org/toc/2150-7511ABSTRACT Acinetobacter baumannii is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell division (RND)-type efflux systems to acquired and intrinsic resistance, we constructed, from an entirely sequenced susceptible A. baumannii strain, a set of isogenic mutants overexpressing each system following introduction of a point mutation in their cognate regulator or a deletion for the pump by allelic replacement. Pairwise comparison of every derivative with the parental strain indicated that AdeABC and AdeFGH are tightly regulated and contribute to acquisition of antibiotic resistance when overproduced. AdeABC had a broad substrate range, including β-lactams, fluoroquinolones, tetracyclines-tigecycline, macrolides-lincosamides, and chloramphenicol, and conferred clinical resistance to aminoglycosides. Importantly, when combined with enzymatic resistance to carbapenems and aminoglycosides, this pump contributed in a synergistic fashion to the level of resistance of the host. In contrast, AdeIJK was expressed constitutively and was responsible for intrinsic resistance to the same major drug classes as AdeABC as well as antifolates and fusidic acid. Surprisingly, overproduction of AdeABC and AdeIJK altered bacterial membrane composition, resulting in decreased biofilm formation but not motility. Natural transformation and plasmid transfer were diminished in recipients overproducing AdeABC. It thus appears that alteration in the expression of efflux systems leads to multiple changes in the relationship between the host and its environment, in addition to antibiotic resistance. IMPORTANCE Increased expression of chromosomal genes for RND-type efflux systems plays a major role in bacterial multidrug resistance. Acinetobacter baumannii has recently emerged as an important human pathogen responsible for epidemics of hospital-acquired infections. Besides its remarkable ability to horizontally acquire resistance determinants, it has a broad intrinsic resistance due to low membrane permeability, endogenous resistance genes, and antibiotic efflux. The study of isogenic mutants from a susceptible A. baumannii clinical isolate overproducing or deleted for each of the three major RND-type pumps demonstrated their major contribution to intrinsic resistance and to the synergism between overproduction of an efflux system and acquisition of a resistance gene. We have also shown that modulation of expression of the structural genes for the efflux systems results in numerous alterations in membrane-associated cellular functions, in particular, in a decrease in biofilm formation and resistance gene acquisition.Eun-Jeong YoonYassine Nait ChabaneSylvie GoussardErik SnesrudPatrice CourvalinEmmanuelle DéCatherine Grillot-CourvalinAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 2 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Eun-Jeong Yoon Yassine Nait Chabane Sylvie Goussard Erik Snesrud Patrice Courvalin Emmanuelle Dé Catherine Grillot-Courvalin Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
description	ABSTRACT Acinetobacter baumannii is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell division (RND)-type efflux systems to acquired and intrinsic resistance, we constructed, from an entirely sequenced susceptible A. baumannii strain, a set of isogenic mutants overexpressing each system following introduction of a point mutation in their cognate regulator or a deletion for the pump by allelic replacement. Pairwise comparison of every derivative with the parental strain indicated that AdeABC and AdeFGH are tightly regulated and contribute to acquisition of antibiotic resistance when overproduced. AdeABC had a broad substrate range, including β-lactams, fluoroquinolones, tetracyclines-tigecycline, macrolides-lincosamides, and chloramphenicol, and conferred clinical resistance to aminoglycosides. Importantly, when combined with enzymatic resistance to carbapenems and aminoglycosides, this pump contributed in a synergistic fashion to the level of resistance of the host. In contrast, AdeIJK was expressed constitutively and was responsible for intrinsic resistance to the same major drug classes as AdeABC as well as antifolates and fusidic acid. Surprisingly, overproduction of AdeABC and AdeIJK altered bacterial membrane composition, resulting in decreased biofilm formation but not motility. Natural transformation and plasmid transfer were diminished in recipients overproducing AdeABC. It thus appears that alteration in the expression of efflux systems leads to multiple changes in the relationship between the host and its environment, in addition to antibiotic resistance. IMPORTANCE Increased expression of chromosomal genes for RND-type efflux systems plays a major role in bacterial multidrug resistance. Acinetobacter baumannii has recently emerged as an important human pathogen responsible for epidemics of hospital-acquired infections. Besides its remarkable ability to horizontally acquire resistance determinants, it has a broad intrinsic resistance due to low membrane permeability, endogenous resistance genes, and antibiotic efflux. The study of isogenic mutants from a susceptible A. baumannii clinical isolate overproducing or deleted for each of the three major RND-type pumps demonstrated their major contribution to intrinsic resistance and to the synergism between overproduction of an efflux system and acquisition of a resistance gene. We have also shown that modulation of expression of the structural genes for the efflux systems results in numerous alterations in membrane-associated cellular functions, in particular, in a decrease in biofilm formation and resistance gene acquisition.
format	article
author	Eun-Jeong Yoon Yassine Nait Chabane Sylvie Goussard Erik Snesrud Patrice Courvalin Emmanuelle Dé Catherine Grillot-Courvalin
author_facet	Eun-Jeong Yoon Yassine Nait Chabane Sylvie Goussard Erik Snesrud Patrice Courvalin Emmanuelle Dé Catherine Grillot-Courvalin
author_sort	Eun-Jeong Yoon
title	Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_short	Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_full	Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_fullStr	Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_full_unstemmed	Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>
title_sort	contribution of resistance-nodulation-cell division efflux systems to antibiotic resistance and biofilm formation in <named-content content-type="genus-species">acinetobacter baumannii</named-content>
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/087e00b022194642a80116adf350c7b8
work_keys_str_mv	AT eunjeongyoon contributionofresistancenodulationcelldivisioneffluxsystemstoantibioticresistanceandbiofilmformationinnamedcontentcontenttypegenusspeciesacinetobacterbaumanniinamedcontent AT yassinenaitchabane contributionofresistancenodulationcelldivisioneffluxsystemstoantibioticresistanceandbiofilmformationinnamedcontentcontenttypegenusspeciesacinetobacterbaumanniinamedcontent AT sylviegoussard contributionofresistancenodulationcelldivisioneffluxsystemstoantibioticresistanceandbiofilmformationinnamedcontentcontenttypegenusspeciesacinetobacterbaumanniinamedcontent AT eriksnesrud contributionofresistancenodulationcelldivisioneffluxsystemstoantibioticresistanceandbiofilmformationinnamedcontentcontenttypegenusspeciesacinetobacterbaumanniinamedcontent AT patricecourvalin contributionofresistancenodulationcelldivisioneffluxsystemstoantibioticresistanceandbiofilmformationinnamedcontentcontenttypegenusspeciesacinetobacterbaumanniinamedcontent AT emmanuellede contributionofresistancenodulationcelldivisioneffluxsystemstoantibioticresistanceandbiofilmformationinnamedcontentcontenttypegenusspeciesacinetobacterbaumanniinamedcontent AT catherinegrillotcourvalin contributionofresistancenodulationcelldivisioneffluxsystemstoantibioticresistanceandbiofilmformationinnamedcontentcontenttypegenusspeciesacinetobacterbaumanniinamedcontent
_version_	1718427625134751744

Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in <named-content content-type="genus-species">Acinetobacter baumannii</named-content>

Ejemplares similares