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

Infect Immun. 2020 Dec 15;89(1):e00180-20. doi: 10.1128/IAI.00180-20. Print 2020 Dec 15.

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.

Keywords: Acinetobacter baumannii; cysteine; transcription factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter Infections / microbiology*
  • Acinetobacter baumannii / physiology*
  • Animals
  • Cysteine / metabolism*
  • Disease Models, Animal
  • Energy Metabolism
  • Gene Expression Regulation, Bacterial
  • Mice
  • Multigene Family
  • Protein Binding
  • Protein Multimerization
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Virulence / genetics
  • Virulence Factors / genetics

Substances

  • Transcription Factors
  • Virulence Factors
  • Cysteine