About this item:

48 Views | 28 Downloads

Author Notes:

Philip N. Rather, prather@emory.edu

PR and AT conceptualized and designed the study and experiments. AT carried out all of the experiments except the RNA sequencing, mouse experiments, and electron microscopy. CC performed the mouse experiments and subsequent data analysis. AT analysed all other data with guidance from PR. AT and CC wrote the original manuscript. All authors contributed to the article and approved the submitted version.

We thank Dr. M. Pérez-Varela for critical reading of this manuscript and Drs. K.A. Tipton, S.E. Anderson, J.M. Colquhoun, and M. Pérez-Varela for their valuable input. We are grateful to Dr. Ayush Kumar at the University of Manitoba for providing pUC18T-mini-Tn7T-Apr-LAC. This work was supported in part by the Robert P. Apkarian Integrated Electron Microscopy Core at Emory University, and we especially thank Jeannette Taylor and Dr. Ricardo C. Guerrero for conducting the electron microscopy.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

Research in the PNR Laboratory is supported by T32 AI106699 to AT and NIH R01 AI72219 and R21 AI115183 and Department of Veterans Affairs awards I01 BX001725 and IK6BX004470 to PR.

Research in the DSW Laboratory is supported by a Department of Veteran’s Affairs award BX002788.

DW is also supported by a Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease award. The content expressed herein is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Department of Veterans Affairs.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Microbiology
  • Acinetobacter baumannii
  • AB5075
  • LysR-type transcriptional regulator
  • phenotypic heterogeneity
  • quorum sensing
  • motility
  • polysaccharide capsule
  • virulence
  • RUTHENIUM RED
  • INFECTIONS
  • PRESERVATION
  • EMERGENCE
  • VIRULENCE
  • SURVIVAL

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

Journal Title:

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY

Volume:

Volume 11

Publisher:

, Pages 778331-778331

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2021 Tierney, Chin, Weiss and Rather

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote