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New Advances on Helicobacter pylori Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 17504

Special Issue Editors


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Guest Editor
Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
Interests: study of microbial survival strategies (biofilm, non-cultivable vital state), evaluation of antimicrobial, anti-biofilm and anti-virulence activities of bioactive substances of natural origin; semi-synthesis and innovative biomaterials; the research activity has concerned oral cavity microorganisms; Helicobacter pylori and microorganisms related to chronic wounds (Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans) and lung infections (Mycobacterium abscessus and other fast-growing mycobacteria)
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Guest Editor
Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: antimicrobial; anti-biofilm and anti-virulence activities of natural compounds alone and combined with antibiotics against multi drug-resistant strains (Helicobacter pylori, Staphylococcus spp., Pseudomonas aeruginosa, Candida albicans, Mycobacterium abscessus and other fast-growing mycobacteria)
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
2. Clinical Microbiology and Virology Unit, Careggi University Hospital, 50139 Florence, Italy
Interests: antimicrobial resistance; rapid clinical microbiology; diagnostic stewardship; carbapenem-resistant Gram-negatives; oxazolidinone-resistant Gram-positives
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Helicobacter pylori is a bacterial gastroduodenal pathogen colonizing around 50% of the world population, representing the main cause of chronic gastritis, peptic ulcer disease and gastric cancer.

The IARC classified H. pylori as a type I carcinogen, recommending the treatment of its infection when the bacterium is diagnosed to prevent gastric cancer.

The development of Anti-H.pylori treatment strategies remain a challenge due its high antibiotic resistance; the WHO listed this bacterium among the pathogens for which increasing antibiotic resistance represents a serious threat for human health.

In addition, H. pylori is able to evade and manipulate the host immune system and establish chronic infection, producing biofilms and entering into a dormant state, inducing a tolerant state against antimicrobial drugs. Innovative therapies are thus needed, such as natural substances associated with drugs commonly used in therapy, which demonstrate a capability to act as antibiotic resistance breakers, probiotics, human-derived-peptides and photodynamic therapy, which are well-described in the literature.

This Special Issue will focus on the latest advances in innovative treatments  for H. pylori’s eradication.

Topics of interest include, but are not limited to, the following:

  • Antibiotic resistance breakers in pylori treatment;
  • New strategies against pylori biofilms and dormancy state;
  • New synergic natural compounds/antibiotic association in pylori treatment.

Dr. Mara Di Giulio
Dr. Silvia Di Lodovico
Dr. Alberto Antonelli
Guest Editors

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Helicobacter pylori
  • biofilm and vBNC state
  • innovative antimicrobial strategies
  • anti-virulence action

Published Papers (5 papers)

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Research

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13 pages, 295 KiB  
Article
Helicobacter pylori and Epstein–Barr Virus Co-Infection in Gastric Disease: What Is the Correlation with p53 Mutation, Genes Methylation and Microsatellite Instability in a Cohort of Sicilian Population?
by Anna Giammanco, Rita Anzalone, Nicola Serra, Giuseppa Graceffa, Salvatore Vieni, Nunzia Scibetta, Teresa Rea, Giuseppina Capra and Teresa Fasciana
Int. J. Mol. Sci. 2023, 24(9), 8104; https://doi.org/10.3390/ijms24098104 - 30 Apr 2023
Viewed by 1554
Abstract
Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases. Helicobacter pylori (Hp) and Epstein–Barr virus (EBV) infection has recently been shown to be correlated with these diseases. A cross-sectional study was performed on 100 hospitalized Italian patients with [...] Read more.
Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases. Helicobacter pylori (Hp) and Epstein–Barr virus (EBV) infection has recently been shown to be correlated with these diseases. A cross-sectional study was performed on 100 hospitalized Italian patients with and without gastric diseases. The patients were stratified into four groups. Significant methylation status differences among CDH1, DAPK, COX2, hMLH1 and CDKN2A were observed for coinfected (Hp-EBV group) patients; particularly, a significant presence of COX2 (p = 0.0179) was observed. For microsatellite instability, minor stability was described in the Hp-HBV group (69.23%, p = 0.0456). Finally, for p53 mutation in the EBV group, exon 6 was, significantly, most frequent in comparison to others (p = 0.0124), and in the Hp-EBV group exon 8 was, significantly, most frequent in comparison to others (p < 0.0001). A significant positive relationship was found between patients with infection (Hp, EBV or both) and p53 mutation (rho = 0.383, p = 0.0001), methylation status (rho = 0.432, p < 0.0001) and microsatellite instability (rho = 0.285, p = 0.004). Finally, we observed among infection and methylation status, microsatellite instability, and p53 mutation a significant positive relationship only between infection and methylation status (OR = 3.78, p = 0.0075) and infection and p53 mutation (OR = 6.21, p = 0.0082). According to our analysis, gastric disease in the Sicilian population has different pathways depending on the presence of various factors, including infectious agents such as Hp and EBV and genetic factors of the subject. Full article
(This article belongs to the Special Issue New Advances on Helicobacter pylori Research)
15 pages, 5749 KiB  
Article
Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by Helicobacter pylori
by Kenly Wuputra, Chia-Chen Ku, Jia-Bin Pan, Chung-Jung Liu, Kohsuke Kato, Ying-Chu Lin, Yi-Chang Liu, Chang-Shen Lin, Michael Hsiao, Ming-Hong Tai, Inn-Wen Chong, Huang-Ming Hu, Chao-Hung Kuo, Deng-Chyang Wu and Kazunari K. Yokoyama
Int. J. Mol. Sci. 2023, 24(7), 6567; https://doi.org/10.3390/ijms24076567 - 31 Mar 2023
Cited by 5 | Viewed by 2021
Abstract
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and [...] Read more.
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of H. pylori-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled H. pylori was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of H. pylori did not affect the proliferation of each H. pylori-infected cancer organoid. To clarify the role of HDGF and TNFα secreted from H. pylori-infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of H. pylori, but TNFα decreased the cell viability in H. pylori-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of H. pylori-infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by H. pylori. Recombinant HDGF and TNFα inhibited the development and invasion of H. pylori-infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of H. pylori-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells. Full article
(This article belongs to the Special Issue New Advances on Helicobacter pylori Research)
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16 pages, 5570 KiB  
Article
Helicobacter pylori Dormant States Are Affected by Vitamin C
by Paola Di Fermo, Silvia Di Lodovico, Emanuela Di Campli, Sara D’Arcangelo, Firas Diban, Simonetta D’Ercole, Mara Di Giulio and Luigina Cellini
Int. J. Mol. Sci. 2023, 24(6), 5776; https://doi.org/10.3390/ijms24065776 - 17 Mar 2023
Cited by 3 | Viewed by 2446
Abstract
Helicobacter pylori colonizes human gastric mucosa, overcoming stressful conditions and entering in a dormant state. This study evaluated: (i) H. pylori’s physiological changes from active to viable-but-non-culturable (VBNC) and persister (AP) states, establishing times/conditions; (ii) the ability of vitamin C to interfere [...] Read more.
Helicobacter pylori colonizes human gastric mucosa, overcoming stressful conditions and entering in a dormant state. This study evaluated: (i) H. pylori’s physiological changes from active to viable-but-non-culturable (VBNC) and persister (AP) states, establishing times/conditions; (ii) the ability of vitamin C to interfere with dormancy generation/resuscitation. A dormant state was induced in clinical MDR H. pylori 10A/13 by: nutrient starvation (for VBNC generation), incubating in an unenriched medium (Brucella broth) or saline solution (SS), and (for AP generation) treatment with 10xMIC amoxicillin (AMX). The samples were monitored after 24, 48, and 72 h, 8–14 days by OD600, CFUs/mL, Live/Dead staining, and an MTT viability test. Afterwards, vitamin C was added to the H. pylori suspension before/after the generation of dormant states, and monitoring took place at 24, 48, and 72 h. The VBNC state was generated after 8 days in SS, and the AP state in AMX for 48 h. Vitamin C reduced its entry into a VBNC state. In AP cells, Vitamin C delayed entry, decreasing viable coccal cells and increasing bacillary/U-shaped bacteria. Vitamin C increased resuscitation (60%) in the VBNC state and reduced the aggregates of the AP state. Vitamin C reduced the incidence of dormant states, promoting the resuscitation rate. Pretreatment with Vitamin C could favor the selection of microbial vegetative forms that are more susceptible to H. pylori therapeutical schemes. Full article
(This article belongs to the Special Issue New Advances on Helicobacter pylori Research)
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10 pages, 1610 KiB  
Communication
Bamboo Salt and Triple Therapy Synergistically Inhibit Helicobacter pylori-Induced Gastritis In Vivo: A Preliminary Study
by Tae Ho Lee, Hang Yeon Jeong, Do Yeon An, Haesung Kim, Jeong-Yong Cho, Do Young Hwang, Hyoung Jae Lee, Kyung-Sik Ham and Jae-Hak Moon
Int. J. Mol. Sci. 2022, 23(22), 13997; https://doi.org/10.3390/ijms232213997 - 13 Nov 2022
Viewed by 2421
Abstract
Helicobacter pylori infections are a major cause of gastrointestinal disorders, including gastric ulcers, gastritis, and gastric cancer. Triple therapy, using two antibiotics and a proton pump inhibitor, is recommended for the treatment of H. pylori infections. However, antibiotic resistance in H. pylori is [...] Read more.
Helicobacter pylori infections are a major cause of gastrointestinal disorders, including gastric ulcers, gastritis, and gastric cancer. Triple therapy, using two antibiotics and a proton pump inhibitor, is recommended for the treatment of H. pylori infections. However, antibiotic resistance in H. pylori is an emerging issue. Bamboo salt, a traditional Korean salt made by baking solar sea salt in bamboo barrels, can ameliorate the symptoms of various gastrointestinal diseases. Herein, we compared the anti-H. pylori activity of triple therapy (clarithromycin, metronidazole, and omeprazole), solar salt, and bamboo salt in vivo as a preliminary study. Four-week-old C57BL/6 male mice were inoculated for eight weeks with the H. pylori Sydney Strain 1 (SS-1) and orally administered triple therapy drugs and salts for five days. The transcript levels of the H. pylori-expressed gene CagA and inflammatory cytokines Tnfα and Il-1β significantly decreased in the bamboo salt treated mice than those in the H. pylori-infected control group. This effect was further enhanced by using triple therapy and bamboo salt together. Solar salt caused modest inhibition of H. pylori-induced inflammation. We also demonstrated the synergistic effects of bamboo salt and triple therapy against H. pylori. Thus, bamboo salt may be a potential candidate agent against the treatment of H. pylori-associated gastritis. Full article
(This article belongs to the Special Issue New Advances on Helicobacter pylori Research)
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Review

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19 pages, 1006 KiB  
Review
Helicobacter pylori in the Oral Cavity: Current Evidence and Potential Survival Strategies
by Lin Zhang, Xi Chen, Biao Ren, Xuedong Zhou and Lei Cheng
Int. J. Mol. Sci. 2022, 23(21), 13646; https://doi.org/10.3390/ijms232113646 - 7 Nov 2022
Cited by 17 | Viewed by 8009
Abstract
Helicobacter pylori (H. pylori) is transmitted primarily through the oral–oral route and fecal–oral route. The oral cavity had therefore been hypothesized as an extragastric reservoir of H. pylori, owing to the presence of H. pylori DNA and particular antigens in [...] Read more.
Helicobacter pylori (H. pylori) is transmitted primarily through the oral–oral route and fecal–oral route. The oral cavity had therefore been hypothesized as an extragastric reservoir of H. pylori, owing to the presence of H. pylori DNA and particular antigens in distinct niches of the oral cavity. This bacterium in the oral cavity may contribute to the progression of periodontitis and is associated with a variety of oral diseases, gastric eradication failure, and reinfection. However, the conditions in the oral cavity do not appear to be ideal for H. pylori survival, and little is known about its biological function in the oral cavity. It is critical to clarify the survival strategies of H. pylori to better comprehend the role and function of this bacterium in the oral cavity. In this review, we attempt to analyze the evidence indicating the existence of living oral H. pylori, as well as potential survival strategies, including the formation of a favorable microenvironment, the interaction between H. pylori and oral microorganisms, and the transition to a non-growing state. Further research on oral H. pylori is necessary to develop improved therapies for the prevention and treatment of H. pylori infection. Full article
(This article belongs to the Special Issue New Advances on Helicobacter pylori Research)
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