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Role of the DksA-like protein in the pathogenesis and diverse metabolic activity of Campylobacter jejuni.

ABSTRACT: DksA is well known for its regulatory role in the transcription of rRNA and genes involved in amino acid synthesis in many bacteria. DksA has also been reported to control expression of virulence genes in pathogenic bacteria. Here, we elucidated the roles of a DksA-like protein (CJJ81176_0160, Cj0125c) in the pathogenesis of Campylobacter jejuni. As in other bacteria, transcription of stable RNA was repressed by the DksA-like protein under stress conditions in C. jejuni. Transcriptomic and proteomic analyses of C. jejuni 81-176 and an isogenic mutant lacking the DksA-like protein showed differential expression of many genes involved in amino acid metabolism, iron-related metabolism, and other metabolic reactions. Also, the C. jejuni DksA-like protein mutant exhibited a decreased ability to invade intestinal cells and induce release of interleukin-8 from intestinal cells. These results suggest that the DksA-like protein plays an important regulatory role in diverse metabolic events and the virulence of C. jejuni.

SUBMITTER: Yun J

PROVIDER: S-EPMC2446803 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Role of the DksA-like protein in the pathogenesis and diverse metabolic activity of Campylobacter jejuni.

Yun Jiae J Jeon Byeonghwa B Barton Yi-Wen YW Plummer Paul P Zhang Qijing Q Ryu Sangryeol S

Journal of bacteriology 20080502 13

DksA is well known for its regulatory role in the transcription of rRNA and genes involved in amino acid synthesis in many bacteria. DksA has also been reported to control expression of virulence genes in pathogenic bacteria. Here, we elucidated the roles of a DksA-like protein (CJJ81176_0160, Cj0125c) in the pathogenesis of Campylobacter jejuni. As in other bacteria, transcription of stable RNA was repressed by the DksA-like protein under stress conditions in C. jejuni. Transcriptomic and prote ...[more]

PMID: 18456813

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Project description:Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, relatively little is known about C. jejuni's precise pathogenesis mechanisms, particularly in comparison to other well-studied enteric organisms such as Escherichia coli and Salmonella spp. Altered expression of phosphate genes in a C. jejuni stringent response mutant, together with known correlations between the stringent response, polyphosphate (poly-P), and virulence in other bacteria, led us to investigate the role of poly-P in C. jejuni stress survival and pathogenesis. All sequenced C. jejuni strains harbor a conserved putative polyphosphate kinase 1 predicted to be principally responsible for poly-P synthesis. We generated a targeted ppk1 deletion mutant (Deltappk1) in C. jejuni strain 81-176 and found that Deltappk1, as well as the DeltaspoT stringent response mutant, exhibited low levels of poly-P at all growth stages. In contrast, wild-type C. jejuni poly-P levels increased significantly as the bacteria transitioned from log to stationary phase. Phenotypic analyses revealed that the Deltappk1 mutant was defective for survival during osmotic shock and low-nutrient stress. However, certain phenotypes associated with ppk1 deletion in other bacteria (i.e., motility and oxidative stress) were unaffected in the C. jejuni Deltappk1 mutant, which also displayed an unexpected increase in biofilm formation. The C. jejuni Deltappk1 mutant was also defective for the virulence-associated phenotype of intraepithelial cell survival in a tissue culture infection model and exhibited a striking, dose-dependent chick colonization defect. These results indicate that poly-P utilization and accumulation contribute significantly to C. jejuni pathogenesis and affect its ability to adapt to specific stresses and stringencies. Furthermore, our study demonstrates that poly-P likely plays both similar and unique roles in C. jejuni compared to its roles in other bacteria and that poly-P metabolism is linked to stringent response mechanisms in C. jejuni.

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Role of the DksA-like protein in the pathogenesis and diverse metabolic activity of Campylobacter jejuni.

Publications

Role of the DksA-like protein in the pathogenesis and diverse metabolic activity of Campylobacter jejuni.

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