Dataset Information

Campylobacter gene regulation in C. jejuni

ABSTRACT: The pathogenic bacterium Campylobacter jejuni is the leading cause of bacterial foodborne gastroenteritis worldwide yet it does not grow in the aerobic environment. The paralogues RrpA and RrpB which are members of MarR family of DNA binding proteins have been shown to be important for the survival of C. jejuni under aerobic and redox stress. We report that RrpA is a positive regulator of mdaB, encoding a flavin-dependent quinone reductase. MdaB confers protection to the cell from redox stress mediated by structurally diverse quinones. RrpB negatively regulates the expression of nfrA (Cj1555c), a flavin reductase. NfrA reduces riboflavin at a much higher rate than flavin mononucleotide (FMN),suggesting exogenous free flavins are the natural substrate. Enzymatic activity of MdaB and NfrA towards their substrates revealed both reductases preferred NADPH as an electron donor. DNA-binding and post translational modification analyses showed that the mechanism of RrpA and RrpB DNA binding is likely a cysteine-based redox switch. Complete genome sequences analysis indicated that MdaB is predominant in Campylobacter spp. and the related Helicobacter spp., whilst NfrA is more often found in C. jejuni strains. Quinones and flavins are antimicrobial redox cycling agents secreted by a wide range of cell-types that can form damaging superoxide by one-electron reactions. We propose that MdaB and NfrA production allows a two-electron reduction mechanism to the less toxic quinol forms. These enzymes thus aid the survival and persistence of C. jejuni in the face of toxic compounds from competing microbes.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Campylobacter Jejuni

SUBMITTER: Steven Lynham

LAB HEAD: Fauzy Nasher

PROVIDER: PXD028910 | Pride | 2021-11-03

REPOSITORIES: Pride

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MdaB and NfrA, Two Novel Reductases Important in the Survival and Persistence of the Major Enteropathogen Campylobacter jejuni.

Nasher Fauzy F Taylor Aidan J AJ Elmi Abdi A Lehri Burhan B Ijaz Umer Z UZ Baker Dave D Goram Richard R Lynham Steven S Singh Dipali D Stabler Richard R Kelly David J DJ Gundogdu Ozan O Wren Brendan W BW

Journal of bacteriology 20211004 1

The paralogues RrpA and RrpB, which are members of the MarR family of DNA binding proteins, are important for the survival of the global bacterial foodborne pathogen Campylobacter jejuni under redox stress. We report that RrpA is a positive regulator of mdaB, encoding a flavin-dependent quinone reductase that contributes to the protection from redox stress mediated by structurally diverse quinones, while RrpB negatively regulates the expression of cj1555c (renamed nfrA for N ...[more]

PMID: 34606373

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