Antimicrobial resistance in Helicobacter pylori: a global overview

Glupczynski, Youri

doi:10.1007/978-94-011-4882-5_42

Cited by 48 publications

(55 citation statements)

References 49 publications

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“…The current eradication strategy requires a combination of 2 to 3 antibiotics and a proton pump inhibitor (39). As such, it is necessary to develop other therapeutic alternatives due to ever-increasing concerns about antibiotic resistance (40), the lack of protection against re-infection, the necessity of taking a long-term prescription for complete eradication, and the high cost of therapy. Development of an ␣-L-fucosidase inhibitor as a prophylactic drug or an adjuvant with possible therapeutic applications is certainly considered as a promising approach for the prevention of H. pylori-related diseases.…”

Section: Discussionmentioning

confidence: 99%

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Liu

Huang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Infecting about one-half of the global human population, Helicobacter pylori is well established as the primary cause of gastritis, duodenal ulcer, and gastric cancer. Currently there is no clear information regarding if and how host cells interact with H. pylori, and if such interactions are dependent on the type of gastric disease. Using fluorescently labeled fucose-containing glycoconjugates, we provide evidence observing both the uptake of L-fucose from gastric cancer cells to H. pylori and that human ␣-L-fucosidase 2 (FUCA2) is secreted only under coculture conditions (i.e., host cells infected with H. pylori). Upon depletion of FUCA2 by RNA interference and detection of translocated CagA (a virulence factor of H. pylori) in host cells, FUCA2 was found to be essential for H. pylori adhesion, in particular to the gastric cancer-and duodenal ulcer-specific strains. Additionally FUCA2 was shown to significantly enhance the expression of Lewis x antigen in H. pylori, which is critical for bacterial cell adhesion in the pathogenesis and defense strategy to escape host surveillance. These findings not only demonstrate an important connection between FUCA2 and the adhesion, growth, and pathogenicity of H. pylori, but also support the idea that FUCA2 is a potential target for clinical diagnosis and therapeutic intervention of H. pylori-related diseases.

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Section: Discussionmentioning

confidence: 99%

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Liu

Huang

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…In fact, resistance to MTZ is common among clinically isolated H. pylori, with frequencies ranging from 10% to more than 90%, depending on the geographic region and patient group. 9,10 MTZ resistance is of clinical significance because it decreases the effectiveness of popular and affordable MTZ-containing anti-H. pylori therapies. 11,12 In addition, as MTZ is also used against a wide variety of prokaryotic and eukaryotic pathogens, [13][14][15] understanding the whole range of MTZ resistance mechanisms utilized by H. pylori may shed light on similar pathways in other clinically significant microbes.…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA

Kim¹,

Joo²,

Lee³

et al. 2009

J Antibiot

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Resistance to metronidazole (MTZ) in Helicobacter pylori is associated with mutations in rdxA, encoding an oxygen-insensitive NADPH nitroreductase, and mutations in frxA, encoding a NAD(P)H-flavin oxidoreductase. Despite this association, the strict correlation of MTZ resistance with mutations in rdxA or frxA is still controversial. In this study, rdxA allelic replacement was used to distinguish resistance-associated nucleotide mutations from the natural genetic diversity of H. pylori. Replacement with truncated rdxA resulted in MTZ resistance, whereas replacement with missense-mutated rdxA from resistant clinical isolates failed to yield MTZ resistance. Thus, although truncation of rdxA confers MTZ resistance in G27 H. pylori, MTZ resistance found in other clinical isolates is not due to the identified amino-acid substitutions. Three of our MTZ-resistant clinical isolates expressed functional rdxA and two of these also encoded full-length frxA. Therefore, MTZ resistance can arise in H. pylori possessing functional rdxA, suggesting that other factors are involved in MTZ resistance.

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“…Resistance to metronidazole (MTZ) is common and is important clinically as a primary cause of failure of MTZ-based anti-Helicobacter therapies (for reviews see references 10, 15, and 24). Frequencies of clinical isolates that are MTZ resistant range from only 10% in Japan (25) to 90% or more in India (26), and up to 50% or more of strains in the United States and Western Europe also are resistant (frequency varies among countries) (8,23). These geographic differences probably reflect frequencies of MTZ use against other, mostly parasitic and anaerobic, infections and thus inadvertent MTZ exposure of resident H. pylori strains.…”

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confidence: 99%

Roles of FrxA and RdxA Nitroreductases of Helicobacter pylori in Susceptibility and Resistance to Metronidazole

et al. 2001

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had interpreted that resistance resulted from inactivation either of frxA or rdxA. These two interpretations were tested here. Resistance was defined as efficient colony formation by single cells from diluted cultures rather than as growth responses of more dense inocula on MTZ-containing medium. Tests of three of Kwon's Mtz s strains showed that each was type II, requiring inactivation of both rdxA and frxA to become resistant. In additional tests, derivatives of frxA mutant strains recovered from MTZ-containing medium were found to contain new mutations in rdxA, and frxA inactivation slowed MTZ-induced killing of Mtz s strains. Northern blot analyses indicated that frxA mRNA, and perhaps also rdxA mRNA, were more abundant in type II than in type I strains. We conclude that development of MTZ resistance in H. pylori requires inactivation of rdxA alone or of both rdxA and frxA, depending on bacterial genotype, but rarely, if ever, inactivation of frxA alone, and that H. pylori strains differ in regulation of nitroreductase gene expression. We suggest that such regulatory differences may be significant functionally during human infection.Helicobacter pylori is a genetically diverse bacterial species that chronically infects the stomachs of more than half of all people worldwide. Its long-term carriage is a major cause of chronic gastritis and peptic ulcer disease and is an early risk factor for gastric cancer (for reviews see references 5, 8, 28, and 32). Resistance to metronidazole (MTZ) is common and is important clinically as a primary cause of failure of MTZ-based anti-Helicobacter therapies (for reviews see references 10, 15, and 24). Frequencies of clinical isolates that are MTZ resistant range from only 10% in Japan (25) to 90% or more in India (26), and up to 50% or more of strains in the United States and Western Europe also are resistant (frequency varies among countries) (8, 23). These geographic differences probably reflect frequencies of MTZ use against other, mostly parasitic and anaerobic, infections and thus inadvertent MTZ exposure of resident H. pylori strains. Recent studies have implicated mutations in the chromosomal genes rdxA (HP0954) and frxA (HP0642) in the development of resistance (7,9,14,16,30, 35). These genes encode related nitroreductases that can convert MTZ from a harmless prodrug to products such as hydroxylamine that are both bactericidal and mutagenic (9, 29).There has been disagreement about the quantitative contributions of rdxA and frxA to MTZ susceptibility and resistance. On the one hand, Kwon and associates had concluded that inactivation of either gene by itself could make any typical H. pylori strain resistant to MTZ (Mtz r ) (21), and that following frxA inactivation, growth on MTZ-containing agar was not associated with mutation of rdxA (20). In contrast, we had concluded that rdxA inactivation is usually or always needed for a Mtz s strain to become Mtz r (16,17). Two types of Mtz s strains were distinguished, however, based on relative levels of FrxA nitroreductase...

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Antimicrobial resistance in Helicobacter pylori: a global overview

Cited by 48 publications

References 49 publications

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Role for α- l -fucosidase in the control of Helicobacter pylori -infected gastric cancer cells

Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA

Roles of FrxA and RdxA Nitroreductases of Helicobacter pylori in Susceptibility and Resistance to Metronidazole

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