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Bacterial Infections

GigC, a LysR Family Transcription Regulator, Is Required for Cysteine Metabolism and Virulence in Acinetobacter baumannii

Michael J. Gebhardt, Daniel M. Czyz, Shweta Singh, Daniel V. Zurawski, Lev Becker, Howard A. Shuman
Igor E. Brodsky, Editor
Michael J. Gebhardt
aDivision of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts, USA
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Daniel M. Czyz
bDepartment of Microbiology and Cell Science, University of Florida, Gainesville, Florida, USA
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Shweta Singh
cWound Infections Dept., Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
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Daniel V. Zurawski
cWound Infections Dept., Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
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Lev Becker
dBen May Department of Cancer Research, University of Chicago, Chicago, Illinois, USA
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Howard A. Shuman
eDepartment of Microbiology, University of Chicago, Chicago, Illinois, USA
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Igor E. Brodsky
University of Pennsylvania
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DOI: 10.1128/IAI.00180-20
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ABSTRACT

A critical facet of mammalian innate immunity involves the hosts’ attempts to sequester and/or limit the availability of key metabolic products from pathogens. For example, nutritional immunity encompasses host approaches to limit the availability of key heavy metal ions such as zinc and iron. Previously, we identified several hundred genes in a multidrug-resistant isolate of Acinetobacter baumannii that are required for growth and/or survival in the Galleria mellonella infection model. In the present study, we further characterize one of these genes, a LysR family transcription regulator that we previously named GigC. We show that mutant strains lacking gigC have impaired growth in the absence of the amino acid cysteine and that gigC regulates the expression of several genes involved in the sulfur assimilation and cysteine biosynthetic pathways. We further show that cells harboring a deletion of the gigC gene are attenuated in two murine infection models, suggesting that the GigC protein, likely through its regulation of the cysteine biosynthetic pathway, plays a key role in the virulence of A. baumannii.

FOOTNOTES

    • Received 26 March 2020.
    • Returned for modification 9 June 2020.
    • Accepted 11 October 2020.
    • Accepted manuscript posted online 19 October 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

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GigC, a LysR Family Transcription Regulator, Is Required for Cysteine Metabolism and Virulence in Acinetobacter baumannii
Michael J. Gebhardt, Daniel M. Czyz, Shweta Singh, Daniel V. Zurawski, Lev Becker, Howard A. Shuman
Infection and Immunity Dec 2020, 89 (1) e00180-20; DOI: 10.1128/IAI.00180-20

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GigC, a LysR Family Transcription Regulator, Is Required for Cysteine Metabolism and Virulence in Acinetobacter baumannii
Michael J. Gebhardt, Daniel M. Czyz, Shweta Singh, Daniel V. Zurawski, Lev Becker, Howard A. Shuman
Infection and Immunity Dec 2020, 89 (1) e00180-20; DOI: 10.1128/IAI.00180-20
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KEYWORDS

Acinetobacter baumannii
cysteine
transcription factors

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