Review – Treatment of <i>Helicobacter pylori</i> infection 2020

OʼConnor, Anthony; Furuta, Takahisa; Gisbert, Javier P.; O’Morain, C.

doi:10.1111/hel.12743

Cited by 46 publications

(30 citation statements)

References 112 publications

(118 reference statements)

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“…Although H. pylori infection remains often asymptomatic [ 2 ], it is an important cause of peptic ulcer disease, MALT lymphoma, and gastric cancer [ 3 , 4 ], and H. pylori is the only bacterial pathogen considered as a Class I carcinogen [ 5 ]. H. pylori eradication is carried out using either triple or quadruple chemotherapy, in which several antibiotics and antimicrobial compounds including bismuth are combined with a proton pump inhibitor (PPI) [ 6 ]. The increasing development of resistance to antimicrobials used in H. pylori eradication therapies has led to the inclusion of clarithromycin (Cla)-resistant H. pylori as a Priority 2 pathogen in the WHO global priority pathogens list, urging the development of novel antimicrobials to treat the infection [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Targeting of Human and Animal Pathogens of the Helicobacter Genus by Flavodoxin Inhibitors: Efficacy, Synergy, Resistance and Mechanistic Studies

Salillas

Galano‐Frutos

Mahía

et al. 2021

IJMS

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Antimicrobial resistant (AMR) bacteria constitute a global health concern. Helicobacter pylori is a Gram-negative bacterium that infects about half of the human population and is a major cause of peptic ulcer disease and gastric cancer. Increasing resistance to triple and quadruple H. pylori eradication therapies poses great challenges and urges the development of novel, ideally narrow spectrum, antimicrobials targeting H. pylori. Here, we describe the antimicrobial spectrum of a family of nitrobenzoxadiazol-based antimicrobials initially discovered as inhibitors of flavodoxin: an essential H. pylori protein. Two groups of inhibitors are described. One group is formed by narrow-spectrum compounds, highly specific for H. pylori, but ineffective against enterohepatic Helicobacter species and other Gram-negative or Gram-positive bacteria. The second group includes extended-spectrum antimicrobials additionally targeting Gram-positive bacteria, the Gram-negative Campylobacter jejuni, and most Helicobacter species, but not affecting other Gram-negative pathogens. To identify the binding site of the inhibitors in the flavodoxin structure, several H. pylori-flavodoxin variants have been engineered and tested using isothermal titration calorimetry. An initial study of the inhibitors capacity to generate resistances and of their synergism with antimicrobials commonly used in H. pylori eradication therapies is described. The narrow-spectrum inhibitors, which are expected to affect the microbiota less dramatically than current antimicrobial drugs, offer an opportunity to develop new and specific H. pylori eradication combinations to deal with AMR in H. pylori. On the other hand, the extended-spectrum inhibitors constitute a new family of promising antimicrobials, with a potential use against AMR Gram-positive bacterial pathogens.

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Section: Introductionmentioning

confidence: 99%

Selective Targeting of Human and Animal Pathogens of the Helicobacter Genus by Flavodoxin Inhibitors: Efficacy, Synergy, Resistance and Mechanistic Studies

Salillas

Galano‐Frutos

Mahía

et al. 2021

IJMS

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“…Furthermore, CagA suppresses the apoptotic activity of VacA and activates the signaling pathway of the factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), allowing the subsequent overexpression of anti-apoptotic agents, interleukin (IL)-8, and defensins (hβDs). H. pylori causes apoptosis accompanied by increased expression of the pro-apoptotic multi-domain proteins Bax (Bcl-2-associated X protein) and Bak proteins that favor apoptosis, suggesting that Bax and Bak may be important mediators of gastric epithelial cells of apoptosis [68][69][70][71].…”

Section: Figurementioning

confidence: 99%

40 Years of Helicobacter pylori: A Revolution in Biomedical Thought

Charitos

D’Agostino

Topi

et al. 2021

Gastroenterology Insights

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Background: Various microorganisms such as bacteria, virus, and fungi can infect humans and cause not just a simple infection but septic conditions, organ dysfunction, and precancerous conditions or cancer involving various organ systems. After the discovery of the microscope, it was easier to discover and study such microorganisms, as in the case of Helicobacter pylori, a pathogen that was seen in the distant era of the nineteenth century but without being recognized as such. It took 100 years to later discover the pathogenesis and the cancer that this bacterium can cause. Since it was discovered, until today, there has been a continuous search for the understanding of its pathogenetic mechanisms, and the therapeutic approach is continuously updated. Methods: We investigated how diagnosis and therapy were dealt with in the past and how researchers sought to understand, exactly, the pathogenetic biomolecular mechanisms of H. pylori, from the genesis of the infection to the current knowledge, with an analysis of carcinogenic mechanisms in the stomach. We have examined the scientific evolution of the knowledge of the disease over these 40 years in the gastroenterological and pharmacological fields. This was possible through a search in the databases of Medline, the WHO website, the Centers for Disease Control and Prevention (CDC) website, PubMed, and Web of Science to analyze the earlier and the latest data regarding H. pylori. Results: With the scientific discoveries over time, thanks to an increasing number of progressions in scientific research in the analysis of the gastric mucosa, the role of Helicobacter pylori in peptic ulcer, carcinogenesis, and in some forms of gastric lymphoma was revealed. Furthermore, over the years, the biomolecular mechanism involvement in some diseases has also been noted (such as cardiovascular ones), which could affect patients positive for H. pylori. Conclusions: Thanks to scientific and technological advances, the role of the bacterium H. pylori in carcinogenesis has been discovered and demonstrated, and new prospective research is currently attempting to investigate the role of other factors in the stomach and other organs. Cancer from H. pylori infection had a high incidence rate compared to various types of cancer, but in recent years, it is improving thanks to the techniques developed in the detection of the bacterium and the evolution of therapies. Thus, although it has become an increasingly treatable disease, there is still continuous ongoing research in the field of treatment for resistance and pharma compliance. Furthermore, in this field, probiotic therapy is considered a valid adjuvant.

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“…In many developing countries it infects about 80% of the population and in developed countries it infects about 30% [2,3]. H. pylori plays an important role in the pathogenesis of chronic gastritis, peptic ulcer diseases, gastric carcinomas, and gastric marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type [4,5,6,7].…”

Section: Introductionmentioning

confidence: 99%

AcrB is essential for bile acid tolerance in Helicobacter pylori

Minami¹,

Hashikawa²,

Ando³

et al. 2022

GSC Adv. Res. Rev.

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Resistance to bile acids is a necessary ability for bacteria that live in the gastrointestinal tract, such as Helicobacter pylori. The role of the bacterial drug efflux system is important for bile acid tolerance. Using the H. pylori JP26 strain and the JP26AcrB strain deficient in AcrB the relationship between the drug efflux system AcrB and the bile acid tolerance of H. pylori was investigated. Bacterial susceptibility to bile acids was measured by the agar dilution method. To examine the ability to efflux bile acids, the intracellular accumulation of radiolabeled chenodeoxycholic acid was measured with a liquid scintillation counter. To investigate the effect of bile acid on the cell adhesion ability of bacteria, bacteria were attached to AGS cells supplemented with chenodeoxycholic acid, and the number of bacteria was counted. Bile acid resistance was significantly lower in the AcrB mutant than in the wild-type strain. The AcrB mutant strains showed a significant increase in the accumulation of 14C - labeled chenodeoxycholic acid in the bacteria. In terms of attachment to AGS cells, the AcrB mutant was significantly lower than the wild-type strain. Furthermore, the AcrB mutant with chenodeoxycholic acid could not be identified. Our results reveal that H. pylori AcrB plays an important role in bile acid resistance. We also suggest that drugs targeting the AcrB efflux system may be a new treatment for H. pylori.

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Review – Treatment of Helicobacter pylori infection 2020

Cited by 46 publications

References 112 publications

Selective Targeting of Human and Animal Pathogens of the Helicobacter Genus by Flavodoxin Inhibitors: Efficacy, Synergy, Resistance and Mechanistic Studies

Selective Targeting of Human and Animal Pathogens of the Helicobacter Genus by Flavodoxin Inhibitors: Efficacy, Synergy, Resistance and Mechanistic Studies

40 Years of Helicobacter pylori: A Revolution in Biomedical Thought

AcrB is essential for bile acid tolerance in Helicobacter pylori

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