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Microorganisms
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Antibiotic Resistance of Helicobacter pylori
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Antibiotic Resistance of Helicobacter pylori

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 16538

Special Issue Editor

Prof. Dr. Yoshio Yamaoka

E-Mail Website
Guest Editor
Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan
Interests: Helicobacter pylori; gastric cancer; virulence factors; epidemiology; human migration; antibiotics resistance; signal pathways; next generation sequencing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Helicobacter pylori (Hp) is a major human pathogen whose rampant antimicrobial resistance seriously threatens available therapeutic options. Important directions exist to counteract this situation: the implementation of new regimens (e.g., vonoprazan-based regimens, new antibiotics such as oxazolidinone analogues), the wider use of bismuth-containing regimens and adjuvants involving N-acetylcysteine and probiotics, anti-biofilm approaches using anti-biofilm peptides and rhamnolipids, and the development of vaccines against Hp. In addition to these interesting directions, the optimization of present eradication regimens is still conceivable with increased need of antimicrobial susceptibility testing, which is time-consuming, laborious, and unavailable in many countries. Fortunately, there is growing hope for non-invasive tests and whole-genome sequencing (WGS) methods for reliable drug resistance prediction in Hp. Elucidating molecular mechanisms and genetic attributes allowing Hp to survive antimicrobial insult is also a continuous quest.

The aim of this Special Issue is to give an overall picture of all aspects of antimicrobial resistance in Hp, with particular emphasis on innovative approaches to tackle resistance in clinical practice. For this purpose, we welcome the submission of research articles, review articles, and short communications related to the various aspects of antimicrobial resistance in Hp: molecular mechanisms, detection systems, epidemiology, Hp eradication regimens, and prevention and surveillance systems. We believe that this Special Issue will give an updated insight into the exciting field of Hp, and hope that it will bring new insights for research activities.

As Guest Editor of this Special Issue, I look forward to reviewing your submissions and, together, defining the present state of the science.

Prof. Dr. Yoshio Yamaoka
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

  • Helicobacter pylori
  • antimicrobial resistance
  • whole-genome sequencing
  • eradication therapy
  • new regimens
  • vaccines

Published Papers (5 papers)

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Editorial

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7 pages, 490 KiB  
Editorial
Advantages of Whole Genome Sequencing in Mitigating the Helicobacter pylori Antimicrobial Resistance Problem
by Kartika Afrida Fauzia, Ricky Indra Alfaray and Yoshio Yamaoka
Microorganisms 2023, 11(5), 1239; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms11051239 - 08 May 2023
Cited by 5 | Viewed by 1414
Abstract
Helicobacter pylori antimicrobial resistance is a critical public health issue. Typically, antimicrobial resistance epidemiology reports include only the antimicrobial susceptibility test results for H. pylori. However, this phenotypic approach is less capable of answering queries related to resistance mechanisms and specific mutations [...] Read more.
Helicobacter pylori antimicrobial resistance is a critical public health issue. Typically, antimicrobial resistance epidemiology reports include only the antimicrobial susceptibility test results for H. pylori. However, this phenotypic approach is less capable of answering queries related to resistance mechanisms and specific mutations found in particular global regions. Whole genome sequencing can help address these two questions while still offering quality control and is routinely validated against AST standards. A comprehensive understanding of the mechanisms of resistance should improve H. pylori eradication efforts and prevent gastric cancer. Full article
(This article belongs to the Special Issue Antibiotic Resistance of Helicobacter pylori)
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Research

Jump to: Editorial

14 pages, 1107 KiB  
Article
Next-Generation Sequencing-Based Study of Helicobacter pylori Isolates from Myanmar and Their Susceptibility to Antibiotics
by Phawinee Subsomwong, Dalla Doohan, Kartika Afrida Fauzia, Junko Akada, Takashi Matsumoto, Than Than Yee, Kyaw Htet, Langgeng Agung Waskito, Vo Phuoc Tuan, Tomohisa Uchida, Takeshi Matsuhisa and Yoshio Yamaoka
Microorganisms 2022, 10(1), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10010196 - 17 Jan 2022
Cited by 9 | Viewed by 3652
Abstract
Evaluation of Helicobacter pylori resistance to antibiotics is crucial for treatment strategy in Myanmar. Moreover, the genetic mechanisms involved remain unknown. We aimed to investigate the prevalence of H. pylori infection, antibiotic resistance, and genetic mechanisms in Myanmar. One hundred fifty patients from [...] Read more.
Evaluation of Helicobacter pylori resistance to antibiotics is crucial for treatment strategy in Myanmar. Moreover, the genetic mechanisms involved remain unknown. We aimed to investigate the prevalence of H. pylori infection, antibiotic resistance, and genetic mechanisms in Myanmar. One hundred fifty patients from two cities, Mawlamyine (n = 99) and Yangon (n = 51), were recruited. The prevalence of H. pylori infection was 43.3% (65/150). The successfully cultured H. pylori isolates (n = 65) were tested for antibiotic susceptibility to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline by Etest, and the resistance rates were 80%, 33.8%, 7.7%, 4.6%, and 0%, respectively. In the multidrug resistance pattern, the metronidazole–levofloxacin resistance was highest for double-drug resistance (16/19; 84.2%), and all triple-drug resistance (3/3) was clarithromycin–metronidazole–levofloxacin resistance. Twenty-three strains were subjected to next-generation sequencing to study their genetic mechanisms. Interestingly, none of the strains resistant to clarithromycin had well-known mutations in 23S rRNA (e.g., A2142G, A2142C, and A2143G). New type mutation genotypes such as pbp1-A (e.g., V45I, S/R414R), 23S rRNA (e.g., T248C), gyrA (e.g., D210N, K230Q), gyrB (e.g., A584V, N679H), rdxA (e.g., V175I, S91P), and frxA (e.g., L33M) were also detected. In conclusion, the prevalence of H. pylori infection and its antibiotic resistance to metronidazole was high in Myanmar. The H. pylori eradication regimen with classical triple therapy, including amoxicillin and clarithromycin, can be used as the first-line therapy in Myanmar. In addition, next-generation sequencing is a powerful high-throughput method for identifying mutations within antibiotic resistance genes and monitoring the spread of H. pylori antibiotic-resistant strains. Full article
(This article belongs to the Special Issue Antibiotic Resistance of Helicobacter pylori)
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19 pages, 3265 KiB  
Article
In Vitro Effects of Lactobacillus plantarum LN66 and Antibiotics Used Alone or in Combination on Helicobacter pylori Mature Biofilm
by Jianfu Ji and Hong Yang
Microorganisms 2021, 9(2), 424; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9020424 - 18 Feb 2021
Cited by 14 | Viewed by 3100
Abstract
Helicobacter pylori is a gastrointestinal pathogen with high prevalence that harms human health. Studies have shown that H. pylori can form antibiotic-tolerant biofilms, which may interfere with the efficacy of clinical antibiotic therapy. Probiotics can antagonize planktonic and biofilm pathogen cells and thus [...] Read more.
Helicobacter pylori is a gastrointestinal pathogen with high prevalence that harms human health. Studies have shown that H. pylori can form antibiotic-tolerant biofilms, which may interfere with the efficacy of clinical antibiotic therapy. Probiotics can antagonize planktonic and biofilm pathogen cells and thus may play an auxiliary role in H. pylori antibiotic therapy. However, the effects of different probiotic strains and antibiotic combinations on H. pylori biofilms need to be further investigated. We determined the cell viability of H. pylori mature biofilms after treatment with Lactobacillus plantarum LN66 cell-free supernatant (CFS), clarithromycin (CLR), and levofloxacin (LVX) alone or in combination by the XTT method. Biofilm cells were observed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Subsequently, protein and polysaccharide concentrations in biofilm extracellular polymeric substances (EPSs) were quantitatively detected by the Bradford method and the phenol-sulfate method. The results showed that LN66 CFS had an eradication effect on mature H. pylori biofilm. When used in combination with CLR, LN66 CFS significantly attenuated the eradication effect of CLR on biofilms; in contrast, when used in combination with LVX, LN66 CFS enhanced the disrupting effect of LVX. We speculate that the different effects of CFS and antibiotic combinations on biofilms may be related to changes in the content of proteins and polysaccharides in EPS and that the combination of CFS and CLR might promote the secretion of EPS, while the combination of CFS and LVX might have the opposite effect. Accordingly, we suggest that supplementation with L. plantarum LN66 may provide additional help when therapy involving LVX is used for clinical H. pylori biofilm eradication, whereas it may impair CLR efficacy when therapy involving CLR is used. Full article
(This article belongs to the Special Issue Antibiotic Resistance of Helicobacter pylori)
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15 pages, 3238 KiB  
Article
High Antibiotic Resistance of Helicobacter pylori and Its Associated Novel Gene Mutations among the Mongolian Population
by Dashdorj Azzaya, Boldbaatar Gantuya, Khasag Oyuntsetseg, Duger Davaadorj, Takashi Matsumoto, Junko Akada and Yoshio Yamaoka
Microorganisms 2020, 8(7), 1062; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8071062 - 16 Jul 2020
Cited by 18 | Viewed by 3314
Abstract
Mongolia has a high prevalence of Helicobacter pylori infection and the second highest incidence of gastric cancer worldwide. Thus, investigating the prevalence of antibiotic resistance and its underlying genetic mechanism is necessary. We isolated 361 H. pylori strains throughout Mongolia. Agar dilution assays [...] Read more.
Mongolia has a high prevalence of Helicobacter pylori infection and the second highest incidence of gastric cancer worldwide. Thus, investigating the prevalence of antibiotic resistance and its underlying genetic mechanism is necessary. We isolated 361 H. pylori strains throughout Mongolia. Agar dilution assays were used to determine the minimum inhibitory concentrations of five antibiotics; amoxicillin, clarithromycin, metronidazole, levofloxacin, and minocycline. The genetic determinants of antibiotic resistance were identified with next-generation sequencing (NGS) and the CLC Genomics Workbench. The resistance to metronidazole, levofloxacin, clarithromycin, amoxicillin, and minocycline was 78.7%, 41.3%, 29.9%, 11.9% and 0.28%, respectively. Multidrug resistance was identified in 51.3% of the isolates investigated which were further delineated into 9 antimicrobial resistance profiles. A number of known antibiotic resistance mutations were identified including rdxA, frxA (missense, frameshift), gyrA (N87K, A88P, D91G/N/Y), 23S rRNA (A2143G), pbp1A (N562Y), and 16S rRNA (A928C). Furthermore, we detected previously unreported mutations in pbp1A (L610*) and the 23S rRNA gene (A1410G, C1707T, A2167G, C2248T, and C2922T). The degree of antibiotic resistance was high, indicating the insufficiency of standard triple therapy in Mongolia. Full article
(This article belongs to the Special Issue Antibiotic Resistance of Helicobacter pylori)
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16 pages, 504 KiB  
Article
Next-Generation Sequencing of the Whole Bacterial Genome for Tracking Molecular Insight into the Broad-Spectrum Antimicrobial Resistance of Helicobacter pylori Clinical Isolates from the Democratic Republic of Congo
by Evariste Tshibangu-Kabamba, Patrick de Jesus Ngoma-Kisoko, Vo Phuoc Tuan, Takashi Matsumoto, Junko Akada, Yasutoshi Kido, Antoine Tshimpi-Wola, Pascal Tshiamala-Kashala, Steve Ahuka-Mundeke, Dieudonné Mumba Ngoy, Ghislain Disashi-Tumba and Yoshio Yamaoka
Microorganisms 2020, 8(6), 887; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8060887 - 11 Jun 2020
Cited by 25 | Viewed by 4141
Abstract
Antimicrobial susceptibility testing (AST) is increasingly needed to guide the Helicobacter pylori (H. pylori) treatment but remains laborious and unavailable in most African countries. To assess the clinical relevance of bacterial whole genome sequencing (WGS)-based methods for predicting drug susceptibility in [...] Read more.
Antimicrobial susceptibility testing (AST) is increasingly needed to guide the Helicobacter pylori (H. pylori) treatment but remains laborious and unavailable in most African countries. To assess the clinical relevance of bacterial whole genome sequencing (WGS)-based methods for predicting drug susceptibility in African H. pylori, 102 strains isolated from the Democratic Republic of Congo were subjected to the phenotypic AST and next-generation sequencing (NGS). WGS was used to screen for the occurrence of genotypes encoding antimicrobial resistance (AMR). We noted the broad-spectrum AMR of H. pylori (rates from 23.5 to 90.0%). A WGS-based method validated for variant discovery in AMR-related genes (discovery rates of 100%) helped in identifying mutations of key genes statistically related to the phenotypic AMR. These included mutations often reported in Western and Asian populations and, interestingly, several putative AMR-related new genotypes in the pbp1A (e.g., T558S, F366L), gyrA (e.g., A92T, A129T), gyrB (e.g., R579C), and rdxA (e.g., R131_K166del) genes. WGS showed high performance for predicting AST phenotypes, especially for amoxicillin, clarithromycin, and levofloxacin (Youden’s index and Cohen’s Kappa > 0.80). Therefore, WGS is an accurate alternative to the phenotypic AST that provides substantial decision-making information for public health policy makers and clinicians in Africa, while providing insight into AMR mechanisms for researchers. Full article
(This article belongs to the Special Issue Antibiotic Resistance of Helicobacter pylori)
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