scholarly journals Multi-Omics Approach Reveals the Potential Core Vaccine Targets for the Emerging Foodborne Pathogen Campylobacter jejuni

2021 ◽  
Vol 12 ◽  
Author(s):  
Hengchun Cao ◽  
Hanxiao Xu ◽  
Chunhui Ning ◽  
Li Xiang ◽  
Qiufang Ren ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Virulence Factor ◽  
Target Genes ◽  
Bacterial Resistance ◽  
Animal Experiments ◽  
Foodborne Pathogen ◽  
Gene Families ◽  
Intestinal Loop ◽  
Potential Core ◽  
New Vaccines

Campylobacter jejuni is a leading cause of bacterial gastroenteritis in humans around the world. The emergence of bacterial resistance is becoming more serious; therefore, development of new vaccines is considered to be an alternative strategy against drug-resistant pathogen. In this study, we investigated the pangenome of 173 C. jejuni strains and analyzed the phylogenesis and the virulence factor genes. In order to acquire a high-quality pangenome, genomic relatedness was firstly performed with average nucleotide identity (ANI) analyses, and an open pangenome of 8,041 gene families was obtained with the correct taxonomy genomes. Subsequently, the virulence property of the core genome was analyzed and 145 core virulence factor (VF) genes were obtained. Upon functional genomics and immunological analyses, five core VF proteins with high antigenicity were selected as potential core vaccine targets for humans. Furthermore, functional annotations indicated that these proteins are involved in important molecular functions and biological processes, such as adhesion, regulation, and secretion. In addition, transcriptome analysis in human cells and pig intestinal loop proved that these vaccine target genes are important in the virulence of C. jejuni in different hosts. Comprehensive pangenome and relevant animal experiments will facilitate discovering the potential core vaccine targets with improved efficiency in reverse vaccinology. Likewise, this study provided some insights into the genetic polymorphism and phylogeny of C. jejuni and discovered potential vaccine candidates for humans. Prospective development of new vaccines using the targets will be an alternative to the use of antibiotics and prevent the development of multidrug-resistant C. jejuni in humans and even other animals.

scholarly journals The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas M. Negretti ◽  
Christopher R. Gourley ◽  
Prabhat K. Talukdar ◽  
Geremy Clair ◽  
Courtney M. Klappenbach ◽  
...  
Keyword(s):  
Host Cell ◽  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Small Gtpase ◽  
Host Cells ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Cell Binding ◽  
Actin Reorganization ◽  
Cell Cytosol

AbstractCampylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

scholarly journals Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers

2014 ◽  
Vol 16 ◽  
Author(s):  
Hua-Hsi Wu ◽  
Wen-chang Lin ◽  
Kuo-Wang Tsai
Keyword(s):  
Gastric Cancer ◽  
Target Genes ◽  
Tumour Progression ◽  
Gene Families ◽  
Cancer Biomarker ◽  
Molecular Biomarkers ◽  
Cell Physiology ◽  
Protein Antigens ◽  
Clinical Biomarkers ◽  
Gastric Cancer Patients

Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

Identification of Salmonella enterica Serovar Typhimurium Using Specific PCR Primers Obtained by Comparative Genomics in Salmonella Serovars

2006 ◽  
Vol 69 (7) ◽  
pp. 1653-1661 ◽  
Author(s):  
H. J. KIM ◽  
S. H. PARK ◽  
T. H. LEE ◽  
B. H. NAHM ◽  
Y. H. CHUNG ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Salmonella Enterica ◽  
Target Genes ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Foodborne Pathogen ◽  
Pcr Primers ◽  
Genomic Sequences ◽  
Local Alignment ◽  
Serovar Typhimurium ◽  
Salmonella Serovars

Salmonella enterica serovar Typhimurium is a major foodborne pathogen throughout the world. Until now, the specific target genes for the detection and identification of serovar Typhimurium have not been developed. To determine the specific probes for serovar Typhimurium, the genes of serovar Typhimurium LT2 that were expected to be unique were selected with the BLAST (Basic Local Alignment Search Tool) program within GenBank. The selected genes were compared with 11 genomic sequences of various Salmonella serovars by BLAST. Of these selected genes, 10 were expected to be specific to serovar Typhimurium and were not related to virulence factor genes of Salmonella pathogenicity island or to genes of the O and H antigens of Salmonella. Primers for the 10 selected genes were constructed, and PCRs were evaluated with various genomic DNAs of Salmonella and non-Salmonella strains for the specific identification of Salmonella serovar Typhimurium. Among all the primer sets for the 10 genes, STM4497 showed the highest degree of specificity to serovar Typhimurium. In this study, a specific primer set for Salmonella serovar Typhimurium was developed on the basis of the comparison of genomic sequences between Salmonella serovars and was validated with PCR. This method of comparative genomics to select target genes or sequences can be applied to the specific detection of microorganisms.

scholarly journals Campylobacter jejuni Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility

mBio ◽  
2021 ◽  
Author(s):  
Courtney M. Klappenbach ◽  
Nicholas M. Negretti ◽  
Jesse Aaron ◽  
Teng-Leong Chew ◽  
Michael E. Konkel
Keyword(s):  
Epithelial Cells ◽  
Cell Motility ◽  
Host Cell ◽  
Campylobacter Jejuni ◽  
Focal Adhesion ◽  
Foodborne Pathogen ◽  
Focal Adhesions ◽  
Structure And Function ◽  
Content Type ◽  
And Function

Campylobacter jejuni is a major foodborne pathogen that causes severe gastritis. We investigated the dynamics of focal adhesion structure and function in C. jejuni -infected epithelial cells.

scholarly journals The Genome-Sequenced Variant of Campylobacter jejuni NCTC 11168 and the Original Clonal Clinical Isolate Differ Markedly in Colonization, Gene Expression, and Virulence-Associated Phenotypes

2004 ◽  
Vol 186 (2) ◽  
pp. 503-517 ◽  
Author(s):  
Erin C. Gaynor ◽  
Shaun Cawthraw ◽  
Georgina Manning ◽  
Joanna K. MacKichan ◽  
Stanley Falkow ◽  
...  
Keyword(s):  
Clinical Isolate ◽  
Campylobacter Jejuni ◽  
Transcriptional Profiling ◽  
Bacterial Pathogen ◽  
Gene Families ◽  
Subtractive Hybridization ◽  
Laboratory Culture ◽  
Phenotypic Differences ◽  
Culture Cells ◽  
Colonization Potential

ABSTRACT The genome sequence of the enteric bacterial pathogen Campylobacter jejuni NCTC 11168 (11168-GS) was published in 2000, providing a valuable resource for the identification of C. jejuni-specific colonization and virulence factors. Surprisingly, the 11168-GS clone was subsequently found to colonize 1-day-old chicks following oral challenge very poorly compared to other strains. In contrast, we have found that the original clinical isolate from which 11168-GS was derived, 11168-O, is an excellent colonizer of chicks. Other marked phenotypic differences were also identified: 11168-O invaded and translocated through tissue culture cells far more efficiently and rapidly than 11168-GS, was significantly more motile, and displayed a different morphology. Serotyping, multiple high-resolution molecular genotyping procedures, and subtractive hybridization did not yield observable genetic differences between the variants, suggesting that they are clonal. However, microarray transcriptional profiling of these strains under microaerobic and severely oxygen-limited conditions revealed dramatic expression differences for several gene families. Many of the differences were in respiration and metabolism genes and operons, suggesting that adaptation to different oxygen tensions may influence colonization potential. This correlates biologically with our observation that anaerobically priming 11168-GS or aerobically passaging 11168-O caused an increase or decrease, respectively, in colonization compared to the parent strain. Expression differences were also observed for several flagellar genes and other less well-characterized genes that may participate in motility. Targeted sequencing of the sigma factors revealed specific DNA differences undetected by the other genomic methods. These observations highlight the capacity of C. jejuni to adapt to multiple environmental niches, the likelihood that this adaptation involves genetic evolution, and provides the first whole-genome molecular exploration of the effect of laboratory culture and storage on colonization and virulence properties of this pathogen.

scholarly journals Draft Genome Sequences of Multidrug-Resistant Campylobacter jejuni Strains Isolated from Chickens in Central China

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Yiluo Cheng ◽  
Wenting Zhang ◽  
Qin Lu ◽  
Guoyuan Wen ◽  
Qingping Luo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antimicrobial Resistance ◽  
Campylobacter Jejuni ◽  
Draft Genome ◽  
Foodborne Pathogen ◽  
Multidrug Resistant ◽  
Central China ◽  
Genome Sequences ◽  
Genetic Characteristics ◽  
Content Type

Campylobacter jejuni is a major foodborne pathogen that plays an important role in spreading drug resistance. We report the draft genome sequences of two multidrug-resistant C. jejuni isolates which contained similar mutations in the CmeR box. This will improve the understanding of C. jejuni antimicrobial resistance and genetic characteristics.

scholarly journals Genetics behind the Biosynthesis of Nonulosonic Acid-Containing Lipooligosaccharides inCampylobacter coli

2019 ◽  
Vol 201 (8) ◽  
Author(s):  
Alejandra Kolehmainen ◽  
Mirko Rossi ◽  
Jacek Stupak ◽  
Jianjun Li ◽  
Michel Gilbert ◽  
...  
Keyword(s):  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Campylobacter Coli ◽  
Strong Impact ◽  
Large Set ◽  
Content Type ◽  
Donor And Acceptor ◽  
Nonulosonic Acid ◽  
Acute Polyneuropathy

ABSTRACTCampylobacter jejuniandCampylobacter coliare the most common causes of bacterial gastroenteritis in the world. Ganglioside mimicry byC. jejunilipooligosaccharide (LOS) is the triggering factor of Guillain-Barré syndrome (GBS), an acute polyneuropathy. Sialyltransferases from glycosyltransferase family 42 (GT-42) are essential for the expression of ganglioside mimics inC. jejuni. Recently, two novel GT-42 genes,cstIVandcstV, have been identified inC. coli. Despite being present in ∼11% of currently availableC. coligenomes, the biological role ofcstIVandcstVis unknown. In the present investigation, mutation studies with two strains expressing eithercstIVorcstVwere performed and mass spectrometry was used to investigate differences in the chemical composition of LOS. Attempts were made to identify donor and acceptor molecules usingin vitroactivity tests with recombinant GT-42 enzymes. Here we show that CstIV and CstV are involved inC. coliLOS biosynthesis. In particular,cstVis associated with LOS sialylation, whilecstIVis linked to the addition of a diacetylated nonulosonic acid residue.IMPORTANCEDespite the fact thatCampylobacter colia major foodborne pathogen, its glycobiology has been largely neglected. The genetic makeup of theC. colilipooligosaccharide biosynthesis locus was largely unknown until recently.C. coliharbors a large set of genes associated with lipooligosaccharide biosynthesis, including genes for several putative glycosyltransferases involved in the synthesis of sialylated lipooligosaccharide inCampylobacter jejuni. In the present study,C. coliwas found to express lipooligosaccharide structures containing sialic acid and other nonulosonate acids. These findings have a strong impact on our understanding ofC. coliecology, host-pathogen interaction, and pathogenesis.

scholarly journals Intrusive Growth of Phloem Fibers in Flax Stem: Integrated Analysis of miRNA and mRNA Expression Profiles

Plants ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 47 ◽  
Author(s):  
Oleg Gorshkov ◽  
Tatyana Chernova ◽  
Natalia Mokshina ◽  
Natalia Gogoleva ◽  
Dmitry Suslov ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Leucine Zipper ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Families ◽  
Fiber Development ◽  
Integrated Analysis ◽  
Target Point ◽  
Family Protein ◽  
Phloem Fibers

Phloem fibers are important elements of plant architecture and the target product of many fiber crops. A key stage in fiber development is intrusive elongation, the mechanisms of which are largely unknown. Integrated analysis of miRNA and mRNA expression profiles in intrusivelygrowing fibers obtained by laser microdissection from flax (Linum usitatissimum L.) stem revealed all 124 known flax miRNA from 23 gene families and the potential targets of differentially expressed miRNAs. A comparison of the expression between phloem fibers at different developmental stages, and parenchyma and xylem tissues demonstrated that members of miR159, miR166, miR167, miR319, miR396 families were down-regulated in intrusively growing fibers. Some putative target genes of these miRNA families, such as those putatively encoding growth-regulating factors, an argonaute family protein, and a homeobox-leucine zipper family protein were up-regulated in elongating fibers. miR160, miR169, miR390, and miR394 showed increased expression. Changes in the expression levels of miRNAs and their target genes did not match expectations for the majority of predicted target genes. Taken together, poorly understood intrusive fiber elongation, the key process of phloem fiber development, was characterized from a miRNA-target point of view, giving new insights into its regulation.

scholarly journals Partial Proteome Map of Campylobacter Jejuni Strain Nctc11168 by Gel-Free Proteomics Analysis

2014 ◽  
Vol 2 (4) ◽  
pp. 464-477
Author(s):  
Zilun Shi ◽  
Chris Dawson ◽  
Stephen L.W. On ◽  
Malik Altaf Hussain
Keyword(s):  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Brain Heart Infusion ◽  
Cell Protein ◽  
Absolute Quantitation ◽  
Whole Cell ◽  
Itraq Analysis ◽  
Proteomic Approach ◽  
Whole Cell Protein ◽  
Isobaric Tags

A proteome map of the foodborne pathogen Campylobacter jejuni NCTC11168 was analyzed using a state-of-the-art gel-free proteomic approach for the first time. A whole cell protein extract was prepared from the C. jejuni strain NCTC11168 grown in brain heart infusion (BHI) broth at 42°C under microaerobic conditions. A gel-free technique using isobaric tags for relative and absolute quantitation (iTRAQ) was employed to create a protein expression profile of the strain. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to identify the proteins. Protein functionalities were searched to classify them. A total of 235 proteins were identified in the whole cell protein fraction of C. jejuni NCTC11168 cells using iTRAQ analysis. Functional grouping of the identified proteins showed that forty percent of these proteins were associated with energy metabolism, protein synthesis and genetic information processing. iTRAQ was faster, easier and proved more sensitive than two-dimensional gel-based proteomics approaches previously applied to C. jejuni, making it an attractive tool for further studies of cellular physiological response. DOI: http://dx.doi.org/10.3126/ijasbt.v2i4.11253  Int J Appl Sci Biotechnol, Vol. 2(4): 464-477 

scholarly journals Induction of an adaptive tolerance response in the foodborne pathogen,Campylobacter jejuni

2003 ◽  
Vol 223 (1) ◽  
pp. 89-93 ◽  
Author(s):  
Caroline Murphy ◽  
Cyril Carroll ◽  
Kieran N Jordan
Keyword(s):  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Tolerance Response
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