Dataset Information

Cj0371: A Novel Virulence-Associated Gene of Campylobacter jejuni.

ABSTRACT: Campylobacter jejuni is the major cause of human bacterial diarrhea worldwide. Its pathogenic mechanism remains poorly understood. cj0371 is a novel gene that was uncovered using immunoscreening. There have been no previous reports regarding its function. In this study, we constructed an insertion mutant and complement of this gene in C. jejuni and examined changes in virulence. We observed that the cj0371 mutant showed significantly increased invasion and colonization ability. We also investigated the role of cj0371 in motility, chemotaxis, and growth kinetics to further study its function. We found that the cj0371 mutant displays hypermotility, enhanced chemotaxis, and enhanced growth kinetics. In addition, we localized the Cj0371 protein at the poles of C. jejuni by fluorescence microscopy. We present data that collectively significantly proves our hypothesis that cj0371 is a new virulence-associated gene and through the influence of chemotaxis plays a negative role in C. jejuni pathogenicity.

SUBMITTER: Du X

PROVIDER: S-EPMC4944492 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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cj0371: A Novel Virulence-Associated Gene of Campylobacter jejuni.

Du Xueqing X Wang Nan N Ren Fangzhe F Tang Hong H Jiao Xinan X Huang Jinlin J

Frontiers in microbiology 20160714

Campylobacter jejuni is the major cause of human bacterial diarrhea worldwide. Its pathogenic mechanism remains poorly understood. cj0371 is a novel gene that was uncovered using immunoscreening. There have been no previous reports regarding its function. In this study, we constructed an insertion mutant and complement of this gene in C. jejuni and examined changes in virulence. We observed that the cj0371 mutant showed significantly increased invasion and colonization ability. We also investiga ...[more]

PMID: 27471500

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Project description:Campylobacter jejuni is recognized as an important causative agent of bacterial gastroenteritis in the developed world. Despite the identification of several factors contributing to infection, characterization of the virulence strategies employed by C. jejuni remains a significant challenge. Bacterial autotransporter proteins are a major class of secretory proteins in Gram-negative bacteria, and notably, many autotransporter proteins contribute to bacterial virulence. The aim of this study was to characterize the C. jejuni 81116 C8J_1278 gene (capC), predicted to encode an autotransporter protein, and examine the contribution of this factor to virulence of C. jejuni The predicted CapC protein has a number of features that are consistent with autotransporters, including the N-terminal signal sequence and the C-terminal ?-barrel domain and was determined to localize to the outer membrane. Inactivation of the capC gene in C. jejuni 81116 and C. jejuni M1 resulted in reduced insecticidal activity in Galleria mellonella larvae. Furthermore, C. jejuni capC mutants displayed significantly reduced adherence to and invasion of nonpolarized, partially differentiated Caco-2 and T84 intestinal epithelial cells. Gentamicin treatment showed that the reduced invasion of the capC mutant is primarily caused by reduced adherence to intestinal epithelial cells, not by reduced invasion capability. C. jejuni capC mutants caused reduced interleukin 8 (IL-8) secretion from intestinal epithelial cells and elicited a significantly diminished immune reaction in Galleria larvae, indicating that CapC functions as an immunogen. In conclusion, CapC is a new virulence determinant of C. jejuni that contributes to the integral infection process of adhesion to human intestinal epithelial cells.IMPORTANCECampylobacter jejuni is a major causative agent of human gastroenteritis, making this zoonotic pathogen of significant importance to human and veterinary public health worldwide. The mechanisms by which C. jejuni interacts with intestinal epithelial cells and causes disease are still poorly understood due, in part, to the heterogeneity of C. jejuni infection biology. Given the importance of C. jejuni to public health, the need to characterize novel and existing virulence mechanisms is apparent. The significance of our research is in demonstrating the role of CapC, a novel virulence factor in C. jejuni that contributes to adhesion and invasion of the intestinal epithelium, thereby in part, addressing the dearth of knowledge concerning the factors involved in Campylobacter pathogenesis and the variation observed in the severity of human infection.

Project description:Campylobacter jejuni is a highly prevalent food-borne pathogen that causes diarrhoeal disease in humans. A natural zoonotic, it must overcome significant stresses both in vivo and during transmission despite the absence of several traditional stress response genes. Its ability to interact with and invade human intestinal epithelial cells closely correlates with virulence. A C. jejuni microarray-based screen revealed that several known virulence genes and several uncharacterized genes, including spoT, were rapidly upregulated during infection of human epithelial cells. spoT and its homologue relA have been shown in other bacteria to regulate the stringent response, an important stress response that to date had not been demonstrated for C. jejuni. We have found that C. jejuni mounts a stringent response that is regulated by spoT. Detailed analyses of a C. jejuni delta spoT mutant revealed that the stringent response is required for several specific stress, transmission and antibiotic resistance-related phenotypes. These include stationary phase survival, growth and survival under low CO2/high O2 conditions, and rifampicin resistance. A secondary suppressor strain that specifically rescues the low CO2 growth defect of the delta spoT mutant was also isolated. The stringent response additionally proved to be required for the virulence-related phenotypes of adherence, invasion, and intracellular survival in two human epithelial cell culture models of infection; spoT is the first C. jejuni gene shown to participate in longer term survival in epithelial cells. Comparing wt to the delta spoT mutant also revealed a strong correlation between gene expression profiles and phenotype differences observed. Together, these data demonstrate a critical role for the C. jejuni stringent response in multiple aspects of C. jejuni biology and pathogenesis. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set

Dataset Information

Cj0371: A Novel Virulence-Associated Gene of Campylobacter jejuni.

Publications

cj0371: A Novel Virulence-Associated Gene of Campylobacter jejuni.

Similar Datasets

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