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Recent Advances in Campylobacter jejuni and Helicobacter pylori

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 15790

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Special Issue Editor

Prof. Stuart A. Thompson

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Guest Editor

Division of Infectious Diseases, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA
Interests: Campylobacter jejuni; Helicobacter pylori; Pathogenesis; Gene regulation; Post-transcriptional regulation; Cyclic-di-GMP; Biofilms; Infection

Special Issue Information

Dear colleagues,

The class epsilonproteobacteria contains two major human pathogens, Campylobacter jejuni and Helicobacter pylori. C. jejuni is one of the most common bacterial causes of gastroenteritis throughout the world and is responsible for more than 100 million cases of disease and more than 30,000 deaths annually. In addition, serious post-infection sequelae such as Guillain–Barré syndrome and reactive arthritis occur. H. pylori colonizes the stomachs of half of the world’s population. While the majority of H. pylori-colonized persons are asymptomatic, ~10% develop either peptic ulcer disease or gastric cancer due to H. pylori-induced chronic inflammation. Peptic ulcer disease affects 340 million people and is responsible for considerable morbidity and mortality. Gastric cancer is the sixth most prevalent cancer worldwide and the second leading cause of cancer deaths (780,000 deaths annually).

In this Special Issue, we will focus on C. jejuni or H. pylori, in particular topics such as pathogenesis, virulence factors, physiology, gene regulation, host cell signaling, and immune responses.

Prof. Stuart A. Thompson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Campylobacter jejuni
Helicobacter pylori
Infection
Inflammation
Pathogenesis
Gastroenteritis
Gastric cancer

Published Papers (7 papers)

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Research

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14 pages, 3038 KiB

Open AccessArticle

Less Pronounced Immunopathological Responses Following Oral Butyrate Treatment of Campylobacter jejuni-Infected Mice

by Ke Du, Minnja S. Foote, Soraya Mousavi, Agnes Buczkowski, Sebastian Schmidt, Stefan Bereswill and Markus M. Heimesaat

Microorganisms 2022, 10(10), 1953; https://doi.org/10.3390/microorganisms10101953 - 30 Sep 2022

Cited by 7 | Viewed by 1726

Abstract

Given that human Campylobacter jejuni infections are rising globally and antibiotic treatment is not recommended, infected patients would substantially benefit from alternative therapeutic strategies. Short-chain fatty acids such as butyrate are known for their health benefits, including anti-microbial and anti-inflammatory effects. This prompted us to investigate potential disease-alleviating properties of butyrate treatment during acute murine C. jejuni-induced enterocolitis. Therefore, following gut microbiota depletion IL-10^−/− mice were challenged with 10⁹ viable C. jejuni cells by oral gavage and treated with butyrate via the drinking water (22 g/L) starting on day 2 post-infection. As early as day 3 post-infection, butyrate reduced diarrheal severity and frequency in treated mice, whereas on day 6 post-infection, gastrointestinal C. jejuni burdens and the overall clinical outcomes were comparable in butyrate- and placebo-treated cohorts. Most importantly, butyrate treatment dampened intestinal pro-inflammatory immune responses given lower colonic numbers of apoptotic cells and neutrophils, less distinct TNF-α secretion in mesenteric lymph nodes and lower IL-6 and MCP-1 concentrations in the ileum. In conclusion, results of our preclinical intervention study provide evidence that butyrate represents a promising candidate molecule for the treatment of acute campylobacteriosis. Full article

(This article belongs to the Special Issue Recent Advances in Campylobacter jejuni and Helicobacter pylori)

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21 pages, 8620 KiB

Open AccessArticle

The Campylobacter jejuni Response Regulator and Cyclic-Di-GMP Binding CbrR Is a Novel Regulator of Flagellar Motility

by Claudia A. Cox, Marek Bogacz, Faiha M. El Abbar, Darren D. Browning, Brian Y. Hsueh, Chris M. Waters, Vincent T. Lee and Stuart A. Thompson

Microorganisms 2022, 10(1), 86; https://doi.org/10.3390/microorganisms10010086 - 31 Dec 2021

Cited by 8 | Viewed by 2678

Abstract

A leading cause of bacterial gastroenteritis, Campylobacter jejuni is also associated with broad sequelae, including extragastrointestinal conditions such as reactive arthritis and Guillain-Barré Syndrome (GBS). CbrR is a C. jejuni response regulator that is annotated as a diguanylate cyclase (DGC), an enzyme that catalyzes the synthesis of c-di-GMP, a universal bacterial second messenger, from GTP. In C. jejuni DRH212, we constructed an unmarked deletion mutant, cbrR⁻, and complemented mutant, cbrR⁺. Motility assays indicated a hyper-motile phenotype associated with cbrR⁻, whereas motility was deficient in cbrR⁺. The overexpression of CbrR in cbrR⁺ was accompanied by a reduction in expression of FlaA, the major flagellin. Biofilm assays and scanning electron microscopy demonstrated similarities between DRH212 and cbrR⁻; however, cbrR⁺ was unable to form significant biofilms. Transmission electron microscopy showed similar cell morphology between the three strains; however, cbrR⁺ cells lacked flagella. Differential radial capillary action of ligand assays (DRaCALA) showed that CbrR binds GTP and c-di-GMP. Liquid chromatography tandem mass spectrometry detected low levels of c-di-GMP in C. jejuni and in E. coli expressing CbrR. CbrR is therefore a negative regulator of FlaA expression and motility, a critical virulence factor in C. jejuni pathogenesis. Full article

(This article belongs to the Special Issue Recent Advances in Campylobacter jejuni and Helicobacter pylori)

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11 pages, 1184 KiB

Open AccessArticle

Genomic and Phenotypic Characteristics in Geographically Separated Clinical Campylobacter jejuni ST353CC Isolates

by Cecilia Johansson, Christian Kampmann, Anna Nilsson, Johan Dicksved, Lars Engstrand and Hilpi Rautelin

Microorganisms 2021, 9(12), 2540; https://doi.org/10.3390/microorganisms9122540 - 8 Dec 2021

Viewed by 2055

Abstract

Campylobacter jejuni fecal isolates of eight international travelers, 5 of which had traveled to Ecuador and 3 to Bangladesh, were characterized, and the possible relationship between bacterial traits and clinical symptoms was further analyzed. All eight isolates belonged to the same Multi-Locus Sequence Type clonal complex (ST353CC). The three isolates from Bangladesh were all of the same sequence type (ST-9438), and when compared to isolates of various other sequence types, they had a larger quantity of unique genetic content, higher expression levels of some putative virulence genes involved in adhesion and invasion (flpA, ciaB and iamA), and showed higher adhesion levels to human HT-29 colon cancer cells in an in vitro infection model. However, in contrast to the seemingly higher pathogenic potential of these bacterial isolates, travelers infected with the ST-9438 isolates had no or only very mild symptoms, whereas the other individuals, whose bacterial isolates seemed to have less pathogenic potential, generally reported severe symptoms. When studying the 16S rRNA gene-based fecal microbiota in samples collected prior to travel, there was an individual variation in the relative abundance of the three major bacterial phyla Actinobacteria, Bacteroidetes and Firmicutes, but there were no associations between composition and diversity of microbiota and development of severe symptoms from the infection. It remains to be confirmed by larger studies whether an individual’s characteristics such as gut microbiota, might be related to the severity of symptoms in Campylobacter infections. Full article

(This article belongs to the Special Issue Recent Advances in Campylobacter jejuni and Helicobacter pylori)

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17 pages, 3060 KiB

Open AccessArticle

Disease-Alleviating Effects of Peroral Activated Charcoal Treatment in Acute Murine Campylobacteriosis

by Stefan Bereswill, Soraya Mousavi, Dennis Weschka and Markus M. Heimesaat

Microorganisms 2021, 9(7), 1424; https://doi.org/10.3390/microorganisms9071424 - 30 Jun 2021

Cited by 9 | Viewed by 2838

Abstract

Foodborne Campylobacter jejuni infections are on the rise and responsible for worldwide serious health issues. Increasing resistance of C. jejuni strains against antimicrobial treatments, necessitates antibiotics-independent treatment options for acute campylobacteriosis. Activated charcoal (AC) constitutes a long-known and safe compound for the treatment of bacterial enteritis. In this preclinical intervention study, we addressed potential anti-pathogenic and immune-modulatory effects of AC during acute experimental campylobacteriosis. Therefore, microbiota-depleted IL-10^−/− mice were infected with C. jejuni by gavage and challenged with either AC or placebo via the drinking water starting on day 2 post-infection. On day 6 post-infection, AC as compared to placebo-treated mice did not only harbor lower intestinal pathogen loads but also presented with alleviated C. jejuni-induced clinical signs such as diarrhea and wasting symptoms. The improved clinical outcome of AC-treated mice was accompanied by less colonic epithelial cell apoptosis and reduced pro-inflammatory immune responses in the intestinal tract. Notably, AC treatment did not only alleviate intestinal, but also extra-intestinal and systemic immune responses as indicated by dampened pro-inflammatory mediator secretion. Given the anti-pathogenic and immune-modulatory properties of AC in this study, a short-term application of this non-toxic drug constitutes a promising antibiotics-independent option for the treatment of human campylobacteriosis. Full article

(This article belongs to the Special Issue Recent Advances in Campylobacter jejuni and Helicobacter pylori)

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17 pages, 3244 KiB

Open AccessArticle

Garlic Essential Oil as Promising Option for the Treatment of Acute Campylobacteriosis—Results from a Preclinical Placebo-Controlled Intervention Study

by Markus M. Heimesaat, Soraya Mousavi, Dennis Weschka and Stefan Bereswill

Microorganisms 2021, 9(6), 1140; https://doi.org/10.3390/microorganisms9061140 - 25 May 2021

Cited by 10 | Viewed by 2264

Abstract

Since human infections with Campylobacter jejuni including antibiotic-resistant strains are rising worldwide, natural compounds might constitute promising antibiotics-independent treatment options for campylobacteriosis. Since the health-beneficial properties of garlic have been known for centuries, we here surveyed the antimicrobial and immune-modulatory effects of garlic essential oil (EO) in acute experimental campylobacteriosis. Therefore, secondary abiotic IL-10^-/- mice were orally infected with C. jejuni strain 81-176 and garlic-EO treatment via the drinking water was initiated on day 2 post-infection. Mice from the garlic-EO group displayed less severe clinical signs of acute campylobacteriosis as compared to placebo counterparts that were associated with lower ileal C. jejuni burdens on day 6 post-infection. Furthermore, when compared to placebo application, garlic-EO treatment resulted in alleviated colonic epithelia cell apoptosis, in less pronounced C. jejuni induced immune cell responses in the large intestines, in dampened pro-inflammatory mediator secretion in intestinal and extra-intestinal compartments, and, finally, in less frequent translocation of viable pathogens from the intestines to distinct organs. Given its potent immune-modulatory and disease-alleviating effects as shown in our actual preclinical placebo-controlled intervention study, we conclude that garlic-EO may be considered as promising adjunct treatment option for acute campylobacteriosis in humans. Full article

(This article belongs to the Special Issue Recent Advances in Campylobacter jejuni and Helicobacter pylori)

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Review

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10 pages, 688 KiB

Open AccessReview

Campylobacter jejuni Infection, Anti-Ganglioside Antibodies, and Neuropathy

by Norman Latov

Microorganisms 2022, 10(11), 2139; https://doi.org/10.3390/microorganisms10112139 - 28 Oct 2022

Cited by 6 | Viewed by 2371 | Correction

Abstract

Preceding infection with Campylobacter jejuni (Cj) occurs in approximately 30% of patients with Guillain–Barre syndrome (GBS), and the risk of GBS following Cj infection is increased by 77 to 100-fold. GBS is most often of the axonal subtype and is thought to be mediated by IgG antibodies to peripheral nerve gangliosides that are cross reactive with oligosaccharides in the Cj lipopolysaccharides (LPS). The antibodies are thought to be induced by molecular mimicry, where immune reactivity to a cross reactive epitope in the infectious organism and normal tissue can cause autoimmune disease. Clonally restricted IgM antibodies that react with the same oligosaccharides in gangliosides and Cj-LPS are associated with chronic neuropathies of otherwise similar phenotypes. The anti-ganglioside antibodies in GBS are of the IgG1 and IgG3 subclasses, indicating T-cell reactivity to the same antigens that could help disrupt the blood–nerve barrier. Cj infection can activate multiple innate and adoptive pro-inflammatory pathways that can overcome immune tolerance and induce autoimmunity. Elucidation of the specific immune mechanisms involved in the development of the autoantibodies and neuropathy would help our understanding of the relation between infection and autoimmunity and aid in the development of more effective preventive interventions and therapies. Full article

(This article belongs to the Special Issue Recent Advances in Campylobacter jejuni and Helicobacter pylori)

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