scholarly journals CapC, a Novel Autotransporter and Virulence Factor ofCampylobacter jejuni

2018 ◽  
Vol 84 (16) ◽  
Author(s):  
Jai W. Mehat ◽  
Simon F. Park ◽  
Arnoud H. M. van Vliet ◽  
Roberto M. La Ragione
Keyword(s):  
Public Health ◽  
Epithelial Cells ◽  
Campylobacter Jejuni ◽  
Virulence Factor ◽  
Causative Agent ◽  
Galleria Mellonella ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Reduced Adherence

ABSTRACTCampylobacter jejuniis 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 byC. jejuniremains 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 theC. jejuni81116 C8J_1278 gene (capC), predicted to encode an autotransporter protein, and examine the contribution of this factor to virulence ofC. 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 β-barrel domain and was determined to localize to the outer membrane. Inactivation of thecapCgene inC. jejuni81116 andC. jejuniM1 resulted in reduced insecticidal activity inGalleria mellonellalarvae. Furthermore,C. jejuni capCmutants 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 thecapCmutant is primarily caused by reduced adherence to intestinal epithelial cells, not by reduced invasion capability.C. jejuni capCmutants caused reduced interleukin 8 (IL-8) secretion from intestinal epithelial cells and elicited a significantly diminished immune reaction inGallerialarvae, indicating that CapC functions as an immunogen. In conclusion, CapC is a new virulence determinant ofC. jejunithat contributes to the integral infection process of adhesion to human intestinal epithelial cells.IMPORTANCECampylobacter jejuniis a major causative agent of human gastroenteritis, making this zoonotic pathogen of significant importance to human and veterinary public health worldwide. The mechanisms by whichC. jejuniinteracts with intestinal epithelial cells and causes disease are still poorly understood due, in part, to the heterogeneity ofC. jejuniinfection biology. Given the importance ofC. jejunito 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 inC. jejunithat contributes to adhesion and invasion of the intestinal epithelium, thereby in part, addressing the dearth of knowledge concerning the factors involved inCampylobacterpathogenesis and the variation observed in the severity of human infection.

scholarly journals Campylobacter jejuni Translocation across Intestinal Epithelial Cells Is Facilitated by Ganglioside-Like Lipooligosaccharide Structures

2012 ◽  
Vol 80 (9) ◽  
pp. 3307-3318 ◽  
Author(s):  
Rogier Louwen ◽  
Edward E. S. Nieuwenhuis ◽  
Leonie van Marrewijk ◽  
Deborah Horst-Kreft ◽  
Lilian de Ruiter ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Campylobacter Jejuni ◽  
Intestinal Epithelial Cells ◽  
Bacterial Species ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Epithelial Cell Lines ◽  
Severe Gastroenteritis ◽  
Bloody Stools ◽  
Human Nerve

ABSTRACTTranslocation across intestinal epithelial cells is an established pathogenic feature of the zoonotic bacterial speciesCampylobacter jejuni. The number ofC. jejunivirulence factors known to be involved in translocation is limited. In the present study, we investigated whether sialylation ofC. jejunilipooligosaccharide (LOS) structures, generating human nerve ganglioside mimics, is important for intestinal epithelial translocation. We here show thatC. jejuniisolates expressing ganglioside-like LOS bound in larger numbers to the Caco-2 intestinal epithelial cells thanC. jejuniisolates lacking such structures. Next, we found that ganglioside-like LOS facilitated endocytosis of bacteria into Caco-2 cells, as visualized by quantitative microscopy using the early and late endosomal markers early endosome-associated protein 1 (EEA1), Rab5, and lysosome-associated membrane protein 1 (LAMP-1). This increased endocytosis was associated with larger numbers of surviving and translocating bacteria. Next, we found that two different intestinal epithelial cell lines (Caco-2 and T84) responded with an elevated secretion of the T-cell attractant CXCL10 to infection by ganglioside-like LOS-expressingC. jejuniisolates. We conclude thatC. jejunitranslocation across Caco-2 cells is facilitated by ganglioside-like LOS, which is of clinical relevance sinceC. jejuniganglioside-like LOS-expressing isolates are linked with severe gastroenteritis and bloody stools inC. jejuni-infected patients.

scholarly journals Cj1136 Is Required for Lipooligosaccharide Biosynthesis, Hyperinvasion, and Chick Colonization by Campylobacter jejuni

2012 ◽  
Vol 80 (7) ◽  
pp. 2361-2370 ◽  
Author(s):  
Muhammad Afzal Javed ◽  
Shaun A. Cawthraw ◽  
Abiyad Baig ◽  
Jianjun Li ◽  
Alan McNally ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Campylobacter Jejuni ◽  
Intestinal Epithelial Cells ◽  
Sodium Taurocholate ◽  
Sodium Deoxycholate ◽  
Targeted Mutagenesis ◽  
Intestinal Epithelial ◽  
Content Type

ABSTRACTCampylobacter jejuniis a major cause of bacterial food-borne enteritis worldwide, and invasion into intestinal epithelial cells is an important virulence mechanism. Recently we reported the identification of hyperinvasiveC. jejunistrains and created a number of transposon mutants of one of these strains, some of which exhibited reduced invasion into INT-407 and Caco-2 cells. In one such mutant the transposon had inserted into a homologue ofcj1136, which encodes a putative galactosyltransferase according to the annotation of theC. jejuniNCTC11168 genome. In the current study, we investigated the role ofcj1136inC. jejunivirulence, lipooligosaccharide (LOS) biosynthesis, and host colonization by targeted mutagenesis and complementation of the mutation. Thecj1136mutant showed a significant reduction in invasion into human intestinal epithelial cells compared to the wild-type strain 01/51. Invasion levels were partially restored on complementing the mutation. The inactivation ofcj1136resulted in the production of truncated LOS, while biosynthesis of a full-length LOS molecule was restored in the complemented strain. Thecj1136mutant showed an increase in sensitivity to the bile salts sodium taurocholate and sodium deoxycholate and significantly increased sensitivity to polymyxin B compared to the parental strain. Importantly, the ability of the mutant to colonize 1-day-old chicks was also significantly impaired. This study confirms that a putative galactosyltransferase encoded bycj1136is involved in LOS biosynthesis and is important forC. jejunivirulence, as disruption of this gene and the resultant truncation of LOS affect both colonizationin vivoand invasivenessin vitro.

scholarly journals A σ28-Regulated Nonflagella Gene Contributes to Virulence of Campylobacter jejuni 81-176

2006 ◽  
Vol 74 (1) ◽  
pp. 769-772 ◽  
Author(s):  
Scarlett Goon ◽  
Cheryl P. Ewing ◽  
Maria Lorenzo ◽  
Dawn Pattarini ◽  
Gary Majam ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Campylobacter Jejuni ◽  
Diarrheal Disease ◽  
Intestinal Epithelial Cells ◽  
Disease Model ◽  
Intestinal Epithelial ◽  
Model Expression

ABSTRACT A Campylobacter jejuni 81-176 mutant in Cj0977 was fully motile but reduced >3 logs compared to the parent in invasion of intestinal epithelial cells in vitro. The mutant was also attenuated in a ferret diarrheal disease model. Expression of Cj0977 protein was dependent on a minimal flagella structure.

scholarly journals Dual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Mia Madel Alfajaro ◽  
Ji-Yun Kim ◽  
Laure Barbé ◽  
Eun-Hyo Cho ◽  
Jun-Gyu Park ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Blood Group ◽  
Intestinal Epithelial Cells ◽  
Sialic Acids ◽  
Blood Group Antigens ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Group A Rotaviruses ◽  
Group A ◽  
Small Intestinal

ABSTRACTGroup A rotaviruses, an important cause of severe diarrhea in children and young animals, initiate infection via interactions of the VP8* domain of the VP4 spike protein with cell surface sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is also used in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for the VP8* domain of WC3 and its reassortant strains have not yet been identified. In the present study, HBGA- and saliva-binding assays showed that both G6P[5] WC3 and mono-reassortant G4P[5] strains recognized the αGal HBGA. The infectivity of both P[5]-bearing strains was significantly reduced in αGal-free MA-104 cells by pretreatment with a broadly specific neuraminidase or by coincubation with the α2,6-linked SA-specificSambucus nigralectin, but not by the α2,3-linked specific sialidase or byMaackia amurensislectin. Free NeuAc and the αGal trisaccharide also prevented the infectivity of both strains. This indicated that both P[5]-bearing strains utilize α2,6-linked SA as a ligand on MA104 cells. However, the two strains replicated in differentiated bovine small intestinal enteroids and in their human counterparts that lack α2,6-linked SA or αGal HBGA, suggesting that additional or alternative receptors such as integrins, hsp70, and tight-junction proteins bound directly to the VP5* domain can be used by the P[5]-bearing strains to initiate the infection of human cells. In addition, these data also suggested that P[5]-bearing strains have potential for cross-species transmission.IMPORTANCEGroup A rotaviruses initiate infection through the binding of the VP8* domain of the VP4 protein to sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is used as the backbone in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for their P[5] VP8* domain has remained elusive. Using a variety of approaches, we demonstrated that the WC3 and bovine-human mono-reassortant G4P[5] vaccine strains recognize both α2,6-linked SA and αGal HBGA as ligands. Neither ligand is expressed on human small intestinal epithelial cells, explaining the absence of natural human infection by P[5]-bearing strains. However, we observed that the P[5]-bearing WC3 and G4P[5] RotaTeq vaccine strains could still infect human intestinal epithelial cells. Thus, the four P[5] RotaTeq vaccine strains potentially binding to additional alternative receptors may be efficient and effective in providing protection against severe rotavirus disease in human.

scholarly journals Interleukin-7 Produced by Intestinal Epithelial Cells in Response to Citrobacter rodentium Infection Plays a Major Role in Innate Immunity against This Pathogen

2015 ◽  
Vol 83 (8) ◽  
pp. 3213-3223 ◽  
Author(s):  
Wei Zhang ◽  
Jiang-Yuan Du ◽  
Qing Yu ◽  
Jun-O Jin
Keyword(s):  
Epithelial Cells ◽  
Protective Immunity ◽  
Bacterial Infections ◽  
Intestinal Epithelial Cells ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Citrobacter Rodentium ◽  
Content Type ◽  
Interleukin 7

Interleukin-7 (IL-7) engages multiple mechanisms to overcome chronic viral infections, but the role of IL-7 in bacterial infections, especially enteric bacterial infections, remains unclear. Here we characterized the previously unexplored role of IL-7 in the innate immune response to the attaching and effacing bacteriumCitrobacter rodentium.C. rodentiuminfection induced IL-7 production from intestinal epithelial cells (IECs). IL-7 production from IECs in response toC. rodentiumwas dependent on gamma interferon (IFN-γ)-producing NK1.1+cells and IL-12. Treatment with anti-IL-7Rα antibody duringC. rodentiuminfection resulted in a higher bacterial burden, enhanced intestinal damage, and greater weight loss and mortality than observed with the control IgG treatment. IEC-produced IL-7 was only essential for protective immunity againstC. rodentiumduring the first 6 days after infection. An impaired bacterial clearance upon IL-7Rα blockade was associated with a significant decrease in macrophage accumulation and activation in the colon. Moreover,C. rodentium-induced expansion and activation of intestinal CD4+lymphoid tissue inducer (LTi) cells was completely abrogated by IL-7Rα blockade. Collectively, these data demonstrate that IL-7 is produced by IECs in response toC. rodentiuminfection and plays a critical role in the protective immunity against this intestinal attaching and effacing bacterium.

scholarly journals Polyphosphate kinases modulate Campylobacter jejuni outer membrane constituents and alter its capacity to invade and survive in intestinal epithelial cells in vitro

2015 ◽  
Vol 4 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Ruby Pina-Mimbela ◽  
Jesús Arcos Madrid ◽  
Anand Kumar ◽  
Jordi B Torrelles ◽  
Gireesh Rajashekara
Keyword(s):  
Epithelial Cells ◽  
Outer Membrane ◽  
Campylobacter Jejuni ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial

scholarly journals Inhibition of the NF-κB Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius

2011 ◽  
Vol 77 (13) ◽  
pp. 4681-4684 ◽  
Author(s):  
Ghalia Kaci ◽  
Omar Lakhdari ◽  
Joël Doré ◽  
S. Dusko Ehrlich ◽  
Pierre Renault ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Streptococcus Salivarius ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Human Intestinal Epithelial Cells ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTStreptococcus salivariusexhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-α). Supernatant from each strain downregulated NF-κB activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8).

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