The hrcA and hspR regulons of Campylobacter jejuni

Holmes, Christopher W.; Penn, Charles W.; Lund, Peter A.

doi:10.1099/mic.0.031708-0

Cited by 27 publications

(51 citation statements)

References 48 publications

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“…These included upregulated bipartite energy taxis response system genes cetAB and the gene for a putative helix-turn-helix domain containing protein, Cj1533c. Also upregulated continuously was hrcA, encoding a negative regulator of the grpE, dnaK, and groEL heat shock proteins (21).…”

Section: Resultsmentioning

confidence: 99%

Hyperosmotic Stress Response of Campylobacter jejuni

et al. 2012

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The diarrheal pathogen Campylobacter jejuni and other gastrointestinal bacteria encounter changes in osmolarity in the environment, through exposure to food processing, and upon entering host organisms, where osmotic adaptation can be associated with virulence. In this study, growth profiles, transcriptomics, and phenotypic, mutant, and single-cell analyses were used to explore the effects of hyperosmotic stress exposure on C. jejuni. Increased growth inhibition correlated with increased osmotic concentration, with both ionic and nonionic stressors inhibiting growth at 0.620 total osmol liter ؊1 . C. jejuni adaptation to a range of osmotic stressors and concentrations was accompanied by severe filamentation in subpopulations, with microscopy indicating septum formation and phenotypic diversity between individual cells in a filament. Population heterogeneity was also exemplified by the bifurcation of colony morphology into small and large variants on salt stress plates. Flow cytometry of C. jejuni harboring green fluorescent protein (GFP) fused to the ATP synthase promoter likewise revealed bimodal subpopulations under hyperosmotic stress. We also identified frequent hyperosmotic stress-sensitive variants within the clonal wild-type population propagated on standard laboratory medium. Microarray analysis following hyperosmotic upshift revealed enhanced expression of heat shock genes and genes encoding enzymes for synthesis of potential osmoprotectants and cross-protective induction of oxidative stress genes. The capsule export gene kpsM was also upregulated, and an acapsular mutant was defective for growth under hyperosmotic stress. For C. jejuni, an organism lacking most conventional osmotic response factors, these data suggest an unusual hyperosmotic stress response, including likely "bet-hedging" survival strategies relying on the presence of stress-fit individuals in a heterogeneous population.

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Section: Resultsmentioning

confidence: 99%

Hyperosmotic Stress Response of Campylobacter jejuni

et al. 2012

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“…In Escherichia coli, ClpB works with the DnaKGrpE-DnaJ complex to disaggregate misfolded proteins by refolding them (38)(39)(40). In C. jejuni, the transcript level of clpB has been found to be induced following a temperature shift from 37°C to 42°C (41) and is known to be regulated by the heat shock regulator HspR (42). Six other genes encoding heat shock proteins are upregulated by BITC treatment.…”

Section: Survival Of C Jejuni In the Presence Of Bitcmentioning

confidence: 99%

“…Six other genes encoding heat shock proteins are upregulated by BITC treatment. Among them, the genes encoding the heat shock proteins HrcA, DnaK, and GrpE have been suggested to be cotranscribed with and regulated by HspR via the HspR-associated inverted repeat (HAIR) binding site of the hrcA promoter (42). DnaK is a chaperone required for the ClpB-mediated refolding of aggregated proteins (40).…”

Section: Survival Of C Jejuni In the Presence Of Bitcmentioning

confidence: 99%

“…GrpE is a cochaperone required for DnaK activity and a nucleotide exchange factor that allows the release of ADP after ATP hydrolysis by DnaK (43). HrcA is a heat-inducible transcriptional repressor responsible for the regulation of the expression of the GroES/EL chaperones (42). BITC treatment increased the expression level of the groES gene, whereas the groEL gene was also upregulated by BITC treatment but did not appear in our final results due to an expression level increase just under our 1.5-fold-change cutoff value.…”

Section: Survival Of C Jejuni In the Presence Of Bitcmentioning

confidence: 99%

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Insights into the Mode of Action of Benzyl Isothiocyanate on Campylobacter jejuni

Dufour

Ståhl

Rosenfeld

et al. 2013

Appl Environ Microbiol

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cCampylobacter jejuni is a widespread pathogen responsible for most of the food-borne gastrointestinal diseases in Europe. The use of natural antimicrobial molecules is a promising alternative to antibiotic treatments for pathogen control in the food industry. Isothiocyanates are natural antimicrobial compounds, which also display anticancer activity. Several studies described the chemoprotective effect of isothiocyanates on eukaryotic cells, but the antimicrobial mechanism is still poorly understood. We investigated the early cellular response of C. jejuni to benzyl isothiocyanate by both transcriptomic and physiological approaches. The transcriptomic response of C. jejuni to benzyl isothiocyanate showed upregulation of heat shock response genes and an impact on energy metabolism. Oxygen consumption was progressively impaired by benzyl isothiocyanate treatment, as revealed by high-resolution respirometry, while the ATP content increased soon after benzyl isothiocyanate exposition, which suggests a shift in the energy metabolism balance. Finally, benzyl isothiocyanate induced intracellular protein aggregation. These results indicate that benzyl isothiocyanate affects C. jejuni by targeting proteins, resulting in the disruption of major metabolic processes and eventually leading to cell death.

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“…The downregulation of hrcA is accompanied by upregulation of the stress response genes groEL/S. 32 However, the upregulation of these stress response genes (groEL/S) in the stationary phase were not detected in the Dppk1 strain. Regardless, the differential expression of the genes encoding the HrcA family transcriptional regulator and the DnaK chaperone suggest that the ppk1 might contribute to the thermotolerant properties of C. jejuni.…”

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confidence: 92%