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Pathogens
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Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach
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Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: closed (15 February 2022) | Viewed by 23223

Special Issue Editors

Dr. Francesca Sisto

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Guest Editor
Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy
Interests: study of the effects of drugs on the internalization process of Helicobacter pylori; molecular studies of resistance to antimicrobial agents; effect of new molecules against H. pylori in sessile and planktonic form; pathogenicity of H. pylori; antimicrobial susceptibility testing of H. pylori to new synthetized drugs.
Special Issues, Collections and Topics in MDPI journals
Dr. Rossella Grande

E-Mail Website
Guest Editor
Department of Pharmacy, University “G. d'Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
Interests: microbial biofilms; Helicobacter pylori; Lactobacillus reuteri; outer membrane vesicles; extracellular DNA; antimicrobial/antibiofilm activity; human microbiome; probiotics; prebiotics and symbiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Helicobacter pylori is associated with the development of gastritis, peptic and duodenal ulcers, gastric mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. It has been demonstrated that the eradication o H. pylori infection represents an important approach for preventing gastric cancer development.

The persistent increase in resistance versus the antimicrobial drugs commonly used in clinical practice represents one of the biggest concerns of global health. In particular, the resistance rate to clarithromycin is 30% in Italy and Japan, and 40% and 50% in Turkey and China, respectively, so that the resistance against the clarithromycin has been defined by World Health Organization as “a high priority for antibiotic research and development”. Hence, the identification of new therapeutical strategies based on the use of new molecules/compounds of natural origin that do not induce resistance and show efficacy against H. pylori eradication becomes necessary.

The survival and persistence of the microorganism in the human host is due to both its genetic variability and its capability to develop biofilm as well as to enter the viable but nonculturable (VBNC) state. H. pylori develops a well-structured biofilm both in vivo and in vitro. The multifactorial nature of biofilm formation and drug tolerance requires the use of multitarget or combinational therapeutical approaches.

The aim of the present Special Issue is to collect articles focalized on the identification and characterization of (i) New molecules/compounds of natural origin with antibacterial and/or antibiofilm activities used alone or in combination with antimicrobials used in therapy. In particular, it will be of interest to look at biofilm removal strategies/compounds for the eradication of a mature biofilm as well as for the inhibition of biofilm formation to manage H. pylori biofilm infections in clinical practice; (ii) Probiotics or molecules/compounds derived from probiotics as well as the use of postbiotics and symbiotics for the eradication of H. pylori. Submissions of original research articles, commentaries, review articles, opinion articles, or hypothesis and theory articles are encouraged.

Dr. Francesca Sisto
Dr. Rossella Grande
Guest Editors

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. Pathogens 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 2200 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

  • Helicobacter pylori
  • antimicrobial activity
  • antibiofilm activity
  • biofilm
  • probiotics
  • postbiotics
  • symbiotics

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Published Papers (6 papers)

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Research

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17 pages, 5895 KiB  
Article
In Vitro Activity of the Arylaminoartemisinin GC012 against Helicobacter pylori and Its Effects on Biofilm
by Francesca Sisto, Simone Carradori, Sarah D’Alessandro, Nadia Santo, Norma Lattuada, Richard K. Haynes, Donatella Taramelli and Rossella Grande
Pathogens 2022, 11(7), 740; https://doi.org/10.3390/pathogens11070740 - 29 Jun 2022
Cited by 8 | Viewed by 2510
Abstract
This study evaluated the in vitro activity of the arylaminoartemisinin GC012, readily obtained from dihydroartemisinin (DHA), against clinical strains of Helicobacter pylori (H. pylori) with different antibiotic susceptibilities in the planktonic and sessile state. The activity was assessed in terms of [...] Read more.
This study evaluated the in vitro activity of the arylaminoartemisinin GC012, readily obtained from dihydroartemisinin (DHA), against clinical strains of Helicobacter pylori (H. pylori) with different antibiotic susceptibilities in the planktonic and sessile state. The activity was assessed in terms of bacteriostatic and bactericidal potential. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined by the broth microdilution method. After treatment with GC012, all bacterial strains showed significantly lower MIC and MBC values compared to those of DHA. The effect of combination of GC012 with antibiotics was examined using the checkerboard method. GC012 displayed synergistic interactions with metronidazole, clarithromycin, and amoxicillin in all the strains. The antibiofilm activity was evaluated via crystal violet staining, AlamarBlue® assay, colony-forming unit count, and fluorescence microscopy. At ½ MIC and ¼ MIC concentration, both GC012 and DHA inhibited biofilm formation, but only GC012 showed a minimal biofilm eradication concentration (MBEC) on mature biofilm. Furthermore, both compounds induced structural changes in the bacterial membrane, as observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). It is thereby demonstrated that GC012 has the potential to be efficacious against H. pylori infection. Full article
(This article belongs to the Special Issue Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach)
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13 pages, 3728 KiB  
Article
Capsaicin Inhibits Inflammation and Gastric Damage during H pylori Infection by Targeting NF-kB–miRNA Axis
by Kalyani Saha, Deotima Sarkar, Uzma Khan, Bipul Chandra Karmakar, Sangita Paul, Asish K. Mukhopadhyay, Shanta Dutta and Sushmita Bhattacharya
Pathogens 2022, 11(6), 641; https://doi.org/10.3390/pathogens11060641 - 1 Jun 2022
Cited by 12 | Viewed by 3471
Abstract
Helicobacter pylori (H. pylori) infection is considered as one of the strongest risk factors for gastric disorders. Infection triggers several host pathways to elicit inflammation, which further proceeds towards gastric complications. The NF-kB pathway plays a central role in the upregulation of the [...] Read more.
Helicobacter pylori (H. pylori) infection is considered as one of the strongest risk factors for gastric disorders. Infection triggers several host pathways to elicit inflammation, which further proceeds towards gastric complications. The NF-kB pathway plays a central role in the upregulation of the pro-inflammatory cytokines during infection. It also regulates the transcriptional network of several inflammatory cytokine genes. Hence, targeting NF-kB could be an important strategy to reduce pathogenesis. Moreover, treatment of H. pylori needs attention as current therapeutics lack efficacy due to antibiotic resistance, highlighting the need for alternative therapeutic approaches. In this study, we investigated the effects of capsaicin, a known NF-kB inhibitor in reducing inflammation and gastric complications during H. pylori infection. We observed that capsaicin reduced NF-kB activation and upregulation of cytokine genes in an in vivo mice model. Moreover, it affected NF-kB–miRNA interplay to repress inflammation and gastric damages. Capsaicin reduced the expression level of mir21 and mir223 along with the pro-inflammatory cytokines. The repression of miRNA further affected downstream targets such as e-cadherin and Akt. Our data represent the first evidence that treatment with capsaicin inhibits inflammation and induces antimicrobial activity during H. pylori infection. This alternative approach might open a new avenue in treating H. pylori infection, thus reducing gastric problems. Full article
(This article belongs to the Special Issue Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach)
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19 pages, 680 KiB  
Article
The Antimicrobial Properties of Poplar and Aspen–Poplar Propolises and Their Active Components against Selected Microorganisms, including Helicobacter pylori
by Jarosław Widelski, Piotr Okińczyc, Emil Paluch, Tomasz Mroczek, Jakub Szperlik, Magdalena Żuk, Zbigniew Sroka, Zuriyadda Sakipova, Ioanna Chinou, Krystyna Skalicka-Woźniak, Anna Malm and Izabela Korona-Głowniak
Pathogens 2022, 11(2), 191; https://doi.org/10.3390/pathogens11020191 - 31 Jan 2022
Cited by 17 | Viewed by 3242
Abstract
There is a noticeable interest in alternative therapies where the outcome is the eradication of the Gram-negative bacterium, Helicobacter pylori (H. pylori), for the purpose of treating many stomach diseases (chronic gastritis and peptic ulcers) and preventing stomach cancer. It is [...] Read more.
There is a noticeable interest in alternative therapies where the outcome is the eradication of the Gram-negative bacterium, Helicobacter pylori (H. pylori), for the purpose of treating many stomach diseases (chronic gastritis and peptic ulcers) and preventing stomach cancer. It is especially urgent because the mentioned pathogen infects over 50% of the world’s population. Recent studies have shown the potential of natural products, such as medicinal plant and bee products, on the inhibition of H. pylori growth. Propolis is such a bee product, with known antimicrobial activities. The main scope of the study is the determination of the antimicrobial activity of ethanolic extracts from 11 propolis samples (mostly from Poland, Ukraine, Kazakhstan, and Greece) against H. pylori, as well as selected bacterial and yeast species. The most effective against H. pylori was the propolis from Ukraine, with an MIC = 0.02 mg/mL while the rest of samples (except one) had an MIC = 0.03 mg/mL. Moreover, significant antimicrobial activity against Gram+ bacteria (with an MIC of 0.02–2.50 mg/mL) and three yeasts (with an MIC of 0.04–0.63 mg/mL) was also observed. A phytochemical analysis (polyphenolic profile) of the propolis samples, by ultra-high-performance liquid chromatography-diode array detector-mass spectrometry (UPLC-DAD-MS), was performed. An evaluation of the impact of the propolis components on antimicrobial activity, consisting of statistical analyses (principal component analysis (PCA) and hierarchical fuzzy clustering), was then performed. It was observed that the chemical composition characteristics of the poplar propolis correlated with higher antibacterial activity, while that of the poplar and aspen propolis correlated with weaker antibacterial activity. To summarize the activity in vitro, all tested propolis samples indicate that they can be regarded as useful and potent factors in antimicrobial therapies, especially against H. pylori. Full article
(This article belongs to the Special Issue Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach)
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17 pages, 4055 KiB  
Article
Antibiofilm and Antimicrobial-Enhancing Activity of Chelidonium majus and Corydalis cheilanthifolia Extracts against Multidrug-Resistant Helicobacter pylori
by Paweł Krzyżek, Adam Junka, Wojciech Słupski, Arleta Dołowacka-Jóźwiak, Bartosz J. Płachno, Aleksandra Sobiecka, Adam Matkowski, Grzegorz Chodaczek, Tadeusz Płusa, Grażyna Gościniak and Sylwia Zielińska
Pathogens 2021, 10(8), 1033; https://doi.org/10.3390/pathogens10081033 - 16 Aug 2021
Cited by 17 | Viewed by 3624
Abstract
Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of about 60% of people worldwide. The search for new drugs with activity against H. pylori is now a hotspot in the effective and safe control of this bacterium. Therefore, the aim of [...] Read more.
Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of about 60% of people worldwide. The search for new drugs with activity against H. pylori is now a hotspot in the effective and safe control of this bacterium. Therefore, the aim of this research was to determine the antibacterial activity of extracts from selected plants of the Papaveraceae family against planktonic and biofilm forms of the multidrug-resistant clinical strain of H. pylori using a broad spectrum of analytical in vitro methods. It was revealed that among the tested extracts, those obtained from Corydalis cheilanthifolia and Chelidonium majus were the most active, with minimal inhibitory concentrations (MICs) of 64 µg/mL and 128 µg/mL, respectively. High concentrations of both extracts showed cytotoxicity against cell lines of human hepatic origin. Therefore, we attempted to lower their MICs through the use of a synergistic combination with synthetic antimicrobials as well as by applying cellulose as a drug carrier. Using checkerboard assays, we determined that both extracts presented synergistic interactions with amoxicillin (AMX) and 3-bromopyruvate (3-BP) (FICI = 0.5) and additive relationships with sertraline (SER) (FICI = 0.75). The antibiofilm activity of extracts and their combinations with AMX, 3-BP, or SER, was analyzed by two methods, i.e., the microcapillary overgrowth under flow conditions (the Bioflux system) and assessment of the viability of lawn biofilms after exposure to drugs released from bacterial cellulose (BC) carriers. Using both methods, we observed a several-fold decrease in the level of H. pylori biofilm, indicating the ability of the tested compounds to eradicate the microbial biofilm. The obtained results indicate that application of plant-derived extracts from the Papaveraceae family combined with synthetic antimicrobials, absorbed into organic BC carrier, may be considered a promising way of fighting biofilm-forming H. pylori. Full article
(This article belongs to the Special Issue Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach)
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Review

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12 pages, 1141 KiB  
Review
Antimicrobial Effects of Lactoferrin against Helicobacter pylori Infection
by Ichiro Imoto, Taro Yasuma, Corina N. D’Alessandro-Gabazza, Satoko Oka, Moriharu Misaki, Noriyuki Horiki and Esteban C. Gabazza
Pathogens 2023, 12(4), 599; https://doi.org/10.3390/pathogens12040599 - 14 Apr 2023
Cited by 6 | Viewed by 5084
Abstract
Helicobacter (H.) pylori is the primary causative agent of various gastroduodenal diseases. H. pylori is an adapted microorganism that has evolved to survive in the acidic conditions of the human stomach, possessing a natural strategy for colonizing harsh environments. Despite the [...] Read more.
Helicobacter (H.) pylori is the primary causative agent of various gastroduodenal diseases. H. pylori is an adapted microorganism that has evolved to survive in the acidic conditions of the human stomach, possessing a natural strategy for colonizing harsh environments. Despite the implementation of various eradication regimens worldwide, the eradication rate of H. pylori has decreased to less than 80% in recent years due to the emergence of antibiotic-resistant strains. This has posed a significant challenge in treating H. pylori infection, as antibiotic resistance and side effects have become increasingly problematic. Lactoferrin, a member of the transferrin family, is an iron-binding protein with antioxidant, antibacterial, antiviral, and anti-inflammatory properties that promote human health. The concentrations of lactoferrin in the gastric juice and mucosa significantly increase during H. pylori infection and are strongly correlated with the severity of gastric mucosal inflammation. Numerous researchers have studied the antimicrobial properties of lactoferrin both in vitro and in vivo. In addition, recent studies have investigated the addition of oral lactoferrin supplementation to H. pylori eradication therapy, even though monotherapy with lactoferrin does not eradicate the microorganism. In this article, we reviewed the survival strategy of H. pylori to evade the antimicrobial activity of human lactoferrin and explore the potential of lactoferrin in H. pylori eradication therapy. Full article
(This article belongs to the Special Issue Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach)
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Other

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18 pages, 1695 KiB  
Systematic Review
Role of Helicobacter pylori and Other Environmental Factors in the Development of Gastric Dysbiosis
by Uriel Gomez-Ramirez, Pedro Valencia-Mayoral, Sandra Mendoza-Elizalde, Juan Rafael Murillo-Eliosa, Fortino Solórzano Santos, Araceli Contreras-Rodríguez, Gerardo Zúñiga, Pamela Aguilar-Rodea, Verónica Leticia Jiménez-Rojas, Juan Carlos Vigueras Galindo, Marcela Salazar-García and Norma Velázquez-Guadarrama
Pathogens 2021, 10(9), 1203; https://doi.org/10.3390/pathogens10091203 - 16 Sep 2021
Cited by 7 | Viewed by 3986
Abstract
Microbiomes are defined as complex microbial communities, which are mainly composed of bacteria, fungi, and viruses residing in diverse regions of the human body. The human stomach consists of a unique and heterogeneous habitat of microbial communities owing to its anatomical and functional [...] Read more.
Microbiomes are defined as complex microbial communities, which are mainly composed of bacteria, fungi, and viruses residing in diverse regions of the human body. The human stomach consists of a unique and heterogeneous habitat of microbial communities owing to its anatomical and functional characteristics, that allow the optimal growth of characteristic bacteria in this environment. Gastric dysbiosis, which is defined as compositional and functional alterations of the gastric microbiota, can be induced by multiple environmental factors, such as age, diet, multiple antibiotic therapies, proton pump inhibitor abuse, H. pylori status, among others. Although H. pylori colonization has been reported across the world, chronic H. pylori infection may lead to serious consequences; therefore, the infection must be treated. Multiple antibiotic therapy improvements are not always successful because of the lack of adherence to the prescribed antibiotic treatment. However, the abuse of eradication treatments can generate gastric dysbiotic states. Dysbiosis of the gastric microenvironment induces microbial resilience, due to the loss of relevant commensal bacteria and simultaneous colonization by other pathobiont bacteria, which can generate metabolic and physiological changes or even initiate and develop other gastric disorders by non-H. pylori bacteria. This systematic review opens a discussion on the effects of multiple environmental factors on gastric microbial communities. Full article
(This article belongs to the Special Issue Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach)
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