MCOLN1/TRPML1 inhibition - a novel strategy used by Helicobacter pylori to escape autophagic killing and antibiotic eradication therapy in vivo

ABSTRACT Helicobacter pylori chronically infects the gastric mucosa, where it can be found free in mucus, attached to cells, and intracellularly. H. pylori requires iron for growth, but the sources of iron used in vivo are unclear. In previous studies, the inability to culture H. pylori without serum made it difficult to determine which host iron sources might be used by H. pylori. Using iron-deficient, chemically defined medium, we determined that H. pylori can bind and extract iron from hemoglobin, transferrin, and lactoferrin. H. pylori can use both bovine and human versions of both lactoferrin and transferrin, contrary to previous reports. Unlike other pathogens, H. pylori preferentially binds the iron-free forms of transferrin and lactoferrin, which limits its ability to extract iron from normal serum, which is not iron saturated. This novel strategy may have evolved to permit limited growth in host tissue during persistent colonization while excessive injury or iron depletion is prevented.

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Eradication therapy of helicobacteriosis with probiotics, problems, and prospects

Experimental and Clinical Gastroenterology ◽

10.31146/1682-8658-ecg-193-9-60-72 ◽

2021 ◽

pp. 60-72

Author(s):

E. I. Ermolenko ◽

A. S. Molostova ◽

N. S. Gladyshev

Keyword(s):

Helicobacter Pylori ◽

Gastrointestinal Tract ◽

Side Effects ◽

Eradication Therapy ◽

Clinical Effectiveness ◽

Mechanisms Of Action ◽

Stomach Diseases ◽

Probiotic Strains

Currently, there is an urgent question of optimizing the treatment of stomach diseases associated with Helicobacter pylori, due to the increasing resistance of the pathogen to antibiotics and the presence of side effects of standard therapy. To optimize it, it is proposed to use probiotics as an additional or monotherapy. The review presents the results of studies of anti-helicobacter activity by in vitro and in vivo systems, as well as an assessment of the clinical effectiveness of various probiotic strains of microorganisms in eradication therapy. Several mechanisms of action of probiotics in the treatment of HP-related diseases are discussed. The problems and prospects of using personalized therapy of helicobacteriosis with probiotics and autoprobiotics, based on strains obtained from the gastrointestinal tract, are indicated.

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Exposure to Metronidazole In Vivo Readily Induces Resistance in Helicobacter pylori and Reduces the Efficacy of Eradication Therapy in Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.4.777 ◽

1999 ◽

Vol 43 (4) ◽

pp. 777-781 ◽

Cited By ~ 24

Author(s):

Peter J. Jenks ◽

Agnes Labigne ◽

Richard L. Ferrero

Keyword(s):

Helicobacter Pylori ◽

Eradication Therapy ◽

Resistance Mechanisms ◽

Prior Exposure ◽

Separate Experiment ◽

Suitable Model ◽

Resistant Strains ◽

Mixed Populations ◽

H Pylori

ABSTRACT The Helicobacter pylori SS1 mouse model was used to characterize the development of resistance in H. pyloriafter treatment with metronidazole monotherapy and to examine the effect of prior exposure to metronidazole on the efficacy of a metronidazole-containing eradication regimen. Mice colonized with the metronidazole-sensitive H. pyloriSS1 strain were treated for 7 days with either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole once a day or three times per day (TID). In a separate experiment,H. pylori-infected mice were administered either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole TID for 7 days, followed 1 month later by either peptone trypsin broth or the mouse equivalent of 20 mg of omeprazole, 250 mg of clarithromycin, and 400 mg of metronidazole twice a day for 7 days. At least 1 month after the completion of treatment, the mice were sacrificed and their stomachs were cultured for H. pylori. The susceptibilities of isolates to metronidazole were assessed by agar dilution determination of the MICs. Mixed populations of metronidazole-resistant and -sensitive strains were isolated from 70% of mice treated with 400 mg of metronidazole TID. The ratio of resistant to sensitive strains was 1:100, and the MICs for the resistant strains varied from 8 to 64 μg/ml. In the second experiment, H. pylori was eradicated from 70% of mice treated with eradication therapy alone, compared to 25% of mice pretreated with metronidazole (P < 0.01). Mice still infected after treatment with metronidazole and eradication therapy contained mixed populations of metronidazole-resistant and -sensitive isolates in a ratio of 1:25. These results demonstrate thatH. pylori readily acquires resistance to metronidazole in vivo and that prior exposure of the organism to metronidazole is associated with failure of eradication therapy. H. pylori-infected mice provide a suitable model for the study of resistance mechanisms inH. pylori and will be useful in determining optimal regimens for the eradication of resistant strains.

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