Biofilm Demolition and Antibiotic Treatment to Eradicate Resistant Helicobacter pylori: A Clinical Trial

Cammarota, Giovanni; Branca, G.; Ardito, Fausta; Sanguinetti, Maurizio; Ianiro, Gianluca; Cianci, Rossella; Torelli, Riccardo; Masala, Giovanna; Gasbarrini, Antonio; Fadda, Giovanni; Landolfi, Raffaele; Gasbarrini, Giovanni

doi:10.1016/j.cgh.2010.05.006

Cited by 82 publications

(89 citation statements)

References 17 publications

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“…Biofilm formation in H. pylori-infected individuals is well documented (33)(34)(35)(36), and a recent publication identified biofilm formation in an animal model of infection (37). H. pylori colonizes the gastric niche, which is highly acidic; however, H. pylori is a neutrophile and employs several mechanism to neutralize the immediate environment (69).…”

Section: Figmentioning

confidence: 99%

“…Biofilm formation by H. pylori has been demonstrated both in vitro (30)(31)(32) and in vivo (33)(34)(35)(36)(37). While it is unclear exactly what drives biofilm formation in H. pylori, protection from antibiotics and host defenses during infection (35,38,39) and/or protection in putative environmental reservoir (40-43) have been proposed. Basic characterization has shown that in vitro biofilm formation is varied across strains (32) and appears to be induced under conditions, such as serum/nutrient starvation (44,45).…”

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confidence: 99%

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Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation

et al. 2016

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Helicobacter pylori must be able to rapidly respond to fluctuating conditions within the stomach. Despite this need for constant adaptation, H. pylori encodes few regulatory proteins. Of the identified regulators, the ferric uptake regulator (Fur), the nickel response regulator (NikR), and the two-component acid response system (ArsRS) are each paramount to the success of this pathogen. While numerous studies have individually examined these regulatory proteins, little is known about their combined effect. Therefore, we constructed a series of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS. A growth curve analysis revealed minor variation in growth kinetics across the strains; these were most pronounced in the triple mutant and in strains lacking ArsS. Visual analysis showed that strains lacking ArsS formed large aggregates and a biofilm-like matrix at the air-liquid interface. Biofilm quantification using crystal violet assays and visualization via scanning electron microscopy (SEM) showed that all strains lacking ArsS or containing a nonphosphorylatable form of ArsR (ArsR-D52N mutant) formed significantly more biofilm than the wild-type strain. Molecular characterization of biofilm formation showed that strains containing mutations in the ArsRS pathway displayed increased levels of cell aggregation and adherence, both of which are key to biofilm development. Furthermore, SEM analysis revealed prevalent coccoid cells and extracellular matrix formation in the ArsR-D52N, ⌬nikR ⌬arsS, and ⌬fur ⌬nikR ⌬arsS mutant strains, suggesting that these strains may have an exacerbated stress response that further contributes to biofilm formation. Thus, H. pylori ArsRS has a previously unrecognized role in biofilm formation. IMPORTANCEDespite a paucity of regulatory proteins, adaptation is key to the survival of H. pylori within the stomach. While prior studies have focused on individual regulatory proteins, such as Fur, NikR, and ArsRS, few studies have examined the combined effect of these factors. Analysis of isogenic mutant strains that contained all possible single, double, and triple regulatory mutations in Fur, NikR, and ArsS revealed a previously unrecognized role for the acid-responsive two-component system ArsRS in biofilm formation.

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Section: Figmentioning

confidence: 99%

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confidence: 99%

Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation

et al. 2016

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“…This suggests that pronase did not play a direct role in eradication of H. pylori in the stomach. N-Acetyl-Lcysteine, which is a mucolytic agent, has a hydrolysis mechanism similar to that of pronase and has been used in the treatment of H. pylori infection (27,28). In our study, the NACG obtained a 20% (3/15) eradication rate.…”

Section: Discussionmentioning

confidence: 54%

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

Liu

et al. 2014

Antimicrob Agents Chemother

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bThis study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian gerbils infected with H. pylori received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of H. pylori. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (P ‫؍‬ 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in H. pylori eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on H. pylori collectively. Thus, pronase may enhance the level of antibiotics for eradication of H. pylori in the clinic.

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“…As a result, patients often do not complete the treatment course, thus generating suboptimal antibiotic blood concentrations that predispose to the selection and survival of resistant bacterial strains [6]. Equally important is the fact that H. pylori colonisation of gastric epithelial cells and the mucus gel layer may result in the formation of protective biofilms reported to be more resistant to killing by antibiotics [7]. It therefore becomes imperative for combination therapy to be modified with more potent new agents capable of penetrating or dislodging these structures to enhance the efficacy of therapy.…”

Section: Introductionmentioning

confidence: 99%

Volatile compounds in the stem bark of Sclerocarya birrea (Anacardiaceae) possess antimicrobial activity against drug-resistant strains of Helicobacter pylori

Njume¹,

Afolayan²,

Green³

et al. 2011

International Journal of Antimicrobial Agents

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Biofilm Demolition and Antibiotic Treatment to Eradicate Resistant Helicobacter pylori: A Clinical Trial

Cited by 82 publications

References 17 publications

Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation

Characterization of Key Helicobacter pylori Regulators Identifies a Role for ArsRS in Biofilm Formation

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

Volatile compounds in the stem bark of Sclerocarya birrea (Anacardiaceae) possess antimicrobial activity against drug-resistant strains of Helicobacter pylori

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