Molecular Dissection of the Campylobacter jejuni CadF and FlpA Virulence Proteins in Binding to Host Cell Fibronectin

Talukdar, Prabhat K.; Negretti, Nicholas M.; Turner, Kyrah L; Konkel, Michael E.

doi:10.3390/microorganisms8030389

Cited by 34 publications

(32 citation statements)

References 70 publications

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“…Both CadF and FlpA are necessary for the adhesion of C. jejuni to fibronectin of the host cell, and both proteins are required for the delivery of C. jejuni Cia effector proteins into the cytosol of the host target cells. This subsequently activates MAPK/ERK signaling pathway, which is required for bacterial invasion of the host cell (Talukdar et al 2020). Both fibronectin-binding adhesins act in a nonredundant way (Talukdar et al 2020).…”

Section: Adherencementioning

confidence: 99%

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Campylobacter sp.: Pathogenicity factors and prevention methods—new molecular targets for innovative antivirulence drugs?

Kreling

Falcone

Kehrenberg

et al. 2020

Appl Microbiol Biotechnol

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Infections caused by bacterial species from the genus Campylobacter are one of the four main causes of strong diarrheal enteritis worldwide. Campylobacteriosis, a typical food-borne disease, can range from mild symptoms to fatal illness. About 550 million people worldwide suffer from campylobacteriosis and lethality is about 33 million p.a. This review summarizes the state of the current knowledge on Campylobacter with focus on its specific virulence factors. Using this knowledge, multifactorial prevention strategies can be implemented to reduce the prevalence of Campylobacter in the food chain. In particular, antiadhesive strategies with specific adhesion inhibitors seem to be a promising concept for reducing Campylobacter bacterial load in poultry production. Antivirulence compounds against bacterial adhesion to and/or invasion into the host cells can open new fields for innovative antibacterial agents. Influencing chemotaxis, biofilm formation, quorum sensing, secretion systems, or toxins by specific inhibitors can help to reduce virulence of the bacterium. In addition, the unusual glycosylation of the bacterium, being a prerequisite for effective phase variation and adaption to different hosts, is yet an unexplored target for combating Campylobacter sp. Plant extracts are widely used remedies in developing countries to combat infections with Campylobacter. Therefore, the present review summarizes the use of natural products against the bacterium in an attempt to stimulate innovative research concepts on the manifold still open questions behind Campylobacter towards improved treatment and sanitation of animal vectors, treatment of infected patients, and new strategies for prevention. Key points • Campylobacter sp. is a main cause of strong enteritis worldwide. • Main virulence factors: cytolethal distending toxin, adhesion proteins, invasion machinery. • Strong need for development of antivirulence compounds.

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Section: Adherencementioning

confidence: 99%

“…This subsequently activates MAPK/ERK signaling pathway, which is required for bacterial invasion of the host cell (Talukdar et al 2020). Both fibronectin-binding adhesins act in a nonredundant way (Talukdar et al 2020).…”

Section: Adherencementioning

confidence: 99%

Campylobacter sp.: Pathogenicity factors and prevention methods—new molecular targets for innovative antivirulence drugs?

Kreling

Falcone

Kehrenberg

et al. 2020

Appl Microbiol Biotechnol

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“…Finally, continued investigation of FNBPs is necessary to provide a greater understanding of their diversity and specificity in mediating bacteria-host cell interactions. Please note that following the submission of this article, we submitted a research article on the cooperative interaction of CadF and FlpA in binding to FN and host cells that has been published (Talukdar et al, 2020).…”

Section: Perspective (Summary and Future Directions)mentioning

confidence: 99%

Taking Control: Campylobacter jejuni Binding to Fibronectin Sets the Stage for Cellular Adherence and Invasion

et al. 2020

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Campylobacter jejuni, a foodborne pathogen, is one of the most common bacterial causes of gastroenteritis in the world. Undercooked poultry, raw (unpasteurized) dairy products, untreated water, and contaminated produce are the most common sources associated with infection. C. jejuni establishes a niche in the gut by adhering to and invading epithelial cells, which results in diarrhea with blood and mucus in the stool. The process of colonization is mediated, in part, by surface-exposed molecules (adhesins) that bind directly to host cell ligands or the extracellular matrix (ECM) surrounding cells. In this review, we introduce the known and putative adhesins of the foodborne pathogen C. jejuni. We then focus our discussion on two C. jejuni Microbial Surface Components Recognizing Adhesive Matrix Molecule(s) (MSCRAMMs), termed CadF and FlpA, which have been demonstrated to contribute to C. jejuni colonization and pathogenesis. In vitro studies have determined that these two surface-exposed proteins bind to the ECM glycoprotein fibronectin (FN). In vivo studies have shown that cadF and flpA mutants exhibit impaired colonization of chickens compared to the wildtype strain. Additional studies have revealed that CadF and FlpA stimulate epithelial cell signaling pathways necessary for cell invasion. Interestingly, CadF and FlpA have distinct FN-binding domains, suggesting that the functions of these proteins are nonredundant. In summary, the binding of FN by C. jejuni CadF and FlpA adhesins has been demonstrated to contribute to adherence, invasion, and cell signaling.

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“… 49 The process of cellular invasion by C. jejuni has been coined the ‘binding and effector mechanism’. 50 During the process of cellular invasion, C. jejuni stimulates the release of IL-8 (primarily from the basolateral surface) of cells. 51-53 The increased concentration of IL-8 results in neutrophil influx, and ultimately leads to tissue damage ( Figure 10 ).…”

Section: Discussionmentioning

confidence: 99%

A porcine ligated loop model reveals new insight into the host immune response againstCampylobacter jejuni

Negretti

Malavasi

et al. 2020

Gut Microbes

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The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen's virulence factors and the host immune system. Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide due to its near-ubiquitous zoonotic association with poultry. One of the outstanding questions is to what extent the bacteria are responsible for the diarrheal symptoms via intestinal cell necrosis versus immune cell initiated tissue damage. To determine the stepwise process of inflammation that leads to diarrhea, we used a piglet ligated intestinal loop model to study the intestinal response to C. jejuni. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine. We found that the abundance of neutrophil related proteins increased in the intestinal lumen during C. jejuni infection, including proteins related to neutrophil migration (neutrophil elastase and MMP9), actin reorganization (Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophil proteins also corresponded with increases of the inflammatory cytokines IL-8 and TNF-α. Compared to infection with the C. jejuni wild-type strain, infection with the noninvasive C. jejuni ∆ciaD mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by C. jejuni virulence and that neutrophils are the predominant cell type responding to C. jejuni infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.

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Molecular Dissection of the Campylobacter jejuni CadF and FlpA Virulence Proteins in Binding to Host Cell Fibronectin

Cited by 34 publications

References 70 publications

Campylobacter sp.: Pathogenicity factors and prevention methods—new molecular targets for innovative antivirulence drugs?

Campylobacter sp.: Pathogenicity factors and prevention methods—new molecular targets for innovative antivirulence drugs?

Taking Control: Campylobacter jejuni Binding to Fibronectin Sets the Stage for Cellular Adherence and Invasion

A porcine ligated loop model reveals new insight into the host immune response againstCampylobacter jejuni

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