A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumannii

Acinetobacter baumannii is a multidrug-resistant, Gram-negative nosocomial pathogen that exhibits phenotypic heterogeneity resulting in virulent opaque (VIR-O) and avirulent translucent (AV-T) colony variants. Each variant has a distinct gene expression profile resulting in multiple phenotypic diffe...

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Main Authors: Aimee R. P. Tierney, Chui Yoke Chin, David S. Weiss, Philip N. Rather
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2021.778331/full
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author Aimee R. P. Tierney
Chui Yoke Chin
Chui Yoke Chin
Chui Yoke Chin
Chui Yoke Chin
David S. Weiss
David S. Weiss
David S. Weiss
David S. Weiss
David S. Weiss
Philip N. Rather
Philip N. Rather
author_facet Aimee R. P. Tierney
Chui Yoke Chin
Chui Yoke Chin
Chui Yoke Chin
Chui Yoke Chin
David S. Weiss
David S. Weiss
David S. Weiss
David S. Weiss
David S. Weiss
Philip N. Rather
Philip N. Rather
author_sort Aimee R. P. Tierney
collection DOAJ
description Acinetobacter baumannii is a multidrug-resistant, Gram-negative nosocomial pathogen that exhibits phenotypic heterogeneity resulting in virulent opaque (VIR-O) and avirulent translucent (AV-T) colony variants. Each variant has a distinct gene expression profile resulting in multiple phenotypic differences. Cells interconvert between the VIR-O and AV-T variants at high frequency under laboratory conditions, suggesting that the genetic mechanism underlying the phenotypic switch could be manipulated to attenuate virulence. Therefore, our group has focused on identifying and characterizing genes that regulate this switch, which led to the investigation of ABUW_1132 (1132), a highly conserved gene predicted to encode a LysR-type transcriptional regulator. ABUW_1132 was shown to be a global regulator as the expression of 74 genes was altered ≥ 2-fold in an 1132 deletion mutant. The 1132 deletion also resulted in a 16-fold decrease in VIR-O to AV-T switching, loss of 3-OH-C12-HSL secretion, and reduced surface-associated motility. Further, the deletion of 1132 in the AV-T background caused elevated capsule production, which increased colony opacity and altered the typical avirulent phenotype of translucent cells. These findings distinguish 1132 as a global regulatory gene and advance our understanding of A. baumannii’s opacity-virulence switch.
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spelling doaj.art-d0f5a9cbf7ce4271860b95d9cd3ba0ec2022-12-21T18:37:17ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-11-011110.3389/fcimb.2021.778331778331A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumanniiAimee R. P. Tierney0Chui Yoke Chin1Chui Yoke Chin2Chui Yoke Chin3Chui Yoke Chin4David S. Weiss5David S. Weiss6David S. Weiss7David S. Weiss8David S. Weiss9Philip N. Rather10Philip N. Rather11Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United StatesEmory Vaccine Center, Atlanta, GA, United StatesYerkes National Primate Research Center, Atlanta, GA, United StatesDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United StatesEmory Antibiotic Resistance Center, Atlanta, GA, United StatesEmory Vaccine Center, Atlanta, GA, United StatesYerkes National Primate Research Center, Atlanta, GA, United StatesDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United StatesEmory Antibiotic Resistance Center, Atlanta, GA, United StatesResearch Service, Department of Veterans Affairs, Atlanta Veterans Affairs (VA) Medical Center, Decatur, GA, United StatesDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United StatesResearch Service, Department of Veterans Affairs, Atlanta Veterans Affairs (VA) Medical Center, Decatur, GA, United StatesAcinetobacter baumannii is a multidrug-resistant, Gram-negative nosocomial pathogen that exhibits phenotypic heterogeneity resulting in virulent opaque (VIR-O) and avirulent translucent (AV-T) colony variants. Each variant has a distinct gene expression profile resulting in multiple phenotypic differences. Cells interconvert between the VIR-O and AV-T variants at high frequency under laboratory conditions, suggesting that the genetic mechanism underlying the phenotypic switch could be manipulated to attenuate virulence. Therefore, our group has focused on identifying and characterizing genes that regulate this switch, which led to the investigation of ABUW_1132 (1132), a highly conserved gene predicted to encode a LysR-type transcriptional regulator. ABUW_1132 was shown to be a global regulator as the expression of 74 genes was altered ≥ 2-fold in an 1132 deletion mutant. The 1132 deletion also resulted in a 16-fold decrease in VIR-O to AV-T switching, loss of 3-OH-C12-HSL secretion, and reduced surface-associated motility. Further, the deletion of 1132 in the AV-T background caused elevated capsule production, which increased colony opacity and altered the typical avirulent phenotype of translucent cells. These findings distinguish 1132 as a global regulatory gene and advance our understanding of A. baumannii’s opacity-virulence switch.https://www.frontiersin.org/articles/10.3389/fcimb.2021.778331/fullAcinetobacter baumanniiAB5075LysR-type transcriptional regulatorphenotypic heterogeneityquorum sensingmotility
spellingShingle Aimee R. P. Tierney
Chui Yoke Chin
Chui Yoke Chin
Chui Yoke Chin
Chui Yoke Chin
David S. Weiss
David S. Weiss
David S. Weiss
David S. Weiss
David S. Weiss
Philip N. Rather
Philip N. Rather
A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumannii
Frontiers in Cellular and Infection Microbiology
Acinetobacter baumannii
AB5075
LysR-type transcriptional regulator
phenotypic heterogeneity
quorum sensing
motility
title A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumannii
title_full A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumannii
title_fullStr A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumannii
title_full_unstemmed A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumannii
title_short A LysR-Type Transcriptional Regulator Controls Multiple Phenotypes in Acinetobacter baumannii
title_sort lysr type transcriptional regulator controls multiple phenotypes in acinetobacter baumannii
topic Acinetobacter baumannii
AB5075
LysR-type transcriptional regulator
phenotypic heterogeneity
quorum sensing
motility
url https://www.frontiersin.org/articles/10.3389/fcimb.2021.778331/full
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