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Title: Structural insights into glutathione-mediated activation of the master regulator PrfA in Listeria monocytogenes

Journal Article · · Protein & Cell
 [1];  [1];  [2];  [1]
  1. Chinese Academy of Sciences (CAS), Beijing (China)
  2. Chinese Academy of Sciences (CAS), Beijing (China); Univ. of Chinese Academy of Sciences, Beijing (China)
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Listeria monocytogenes is a Gram-positive and facultative intracellular bacterial pathogen with two distinct lifestyles: saprophytic in the soil and parasitic in host cells. L. monocytogenes can cause a foodborne infection characterized by bacteremia, meningoencephalitis, abortion or neonatal sepsis and a high case-fatality rate. In relation to pathogenesis, the expression of most virulence genes in L. monocytogenes is regulated by the master regulator PrfA, which is a member of the Crp/Fnr family of site-specific DNA-binding transcription regulators. The absolute requirement of PrfA for pathogenesis was shown utilizing L. monocytogenes strains with deletions or loss-of-function mutations within the prfA gene. PrfA activates transcription by binding to a palindromic promoter element termed the PrfA box (tTAACanntGTtAa). Very recently, glutathione (GSH), either generated by bacteria or derived from host cells, was found to be the essential small molecule cofactor of PrfA through allosteric binding to the protein. PrfAG145S, the most well studied constitutively active mutant, was found to be able to completely bypass the requirement for glutathione during infection.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
Chinese Academy of Sciences (CAS); National Natural Science Foundation of China (NSFC)
OSTI ID:
1430353
Journal Information:
Protein & Cell, Journal Name: Protein & Cell Journal Issue: 4 Vol. 8; ISSN 1674-800X
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Structural basis for the allosteric control of the global transcription factor NtcA by the nitrogen starvation signal 2-oxoglutarate journal June 2010
Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria journal December 2016
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Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γ journal February 2010
The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif: Crystal structure of PrfA journal March 2005
The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics journal December 2015
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Regulation of the prfA transcriptional activator of Listeria monocytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread. journal January 1993
Listeria monocytogenes induces IFNβ expression through an IFI16‐, cGAS‐ and STING‐dependent pathway journal June 2014
Glutathione activates virulence gene expression of an intracellular pathogen journal January 2015
Listeria monocytogenes — from saprophyte to intracellular pathogen journal August 2009
Structural basis for the allosteric control of the global transcription factor NtcA by the nitrogen starvation signal 2-oxoglutarate journal June 2010
Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria journal December 2016
Identification of a gene that positively regulates expression of listeriolysin, the major virulence factor of listeria monocytogenes. journal November 1990
Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γ journal February 2010
The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif: Crystal structure of PrfA journal March 2005
Molecular basis of halorespiration control by CprK, a CRP-FNR type transcriptional regulator: How CprK controls halorespiration journal August 2008
The intrinsic cephalosporin resistome of Listeria monocytogenes in the context of stress response, gene regulation, pathogenesis and therapeutics journal December 2015
Structural Basis of Transcription Activation: The CAP-alpha CTD-DNA Complex journal August 2002
Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees journal August 1991
Regulation of the prfA transcriptional activator of Listeria monocytogenes: multiple promoter elements contribute to intracellular growth and cell-to-cell spread. journal January 1993
Coordinate regulation of virulence genes in Listeria monocytogenes requires the product of the prfA gene. journal January 1992
Listeria monocytogenes induces IFNβ expression through an IFI16‐, cGAS‐ and STING‐dependent pathway journal June 2014

Cited By (7)

In silico identification of novel PrfA inhibitors to fight listeriosis: A virtual screening and molecular dynamics studies journal December 2020
Reduce, Induce, Thrive: Bacterial Redox Sensing during Pathogenesis journal September 2018
Thioredoxin A Is Essential for Motility and Contributes to Host Infection of Listeria monocytogenes via Redox Interactions journal June 2017
Prevalence, Genotypic Characteristics and Antibiotic Resistance of Listeria monocytogenes From Retail Foods in Bulk in Zhejiang Province, China journal July 2019
Flick of a switch: regulatory mechanisms allowing Listeria monocytogenes to transition from a saprophyte to a killer journal August 2019
Thioredoxin A Is Essential for Motility and Contributes to Host Infection of Listeria monocytogenes via Redox Interactions journal June 2017
Prevalence, Genotypic Characteristics and Antibiotic Resistance of Listeria monocytogenes From Retail Foods in Bulk in Zhejiang Province, China journal July 2019

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59 BASIC BIOLOGICAL SCIENCES
Broad Spectrum Cephalosporin
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Glutathione
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