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Article: Sequential inactivation of rdxA (hp0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylori

TitleSequential inactivation of rdxA (hp0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylori
Authors
Issue Date2000
PublisherAmerican Society for Microbiology.
Citation
Journal Of Bacteriology, 2000, v. 182 n. 18, p. 5082-5090 How to Cite?
AbstractHelicobacter pylori is a human-pathogenic bacterial species that is subdivided geographically, with different genotypes predominating in different parts of the world. Here we test and extend an earlier conclusion that metronidazole (Mtz) resistance is due to mutation in rdxA (HP0954), which encodes a nitroreductase that converts Mtz from prodrug to bactericidal agent. We found that (i) rdxA genes PCR amplified from 50 representative Mtz(r) strains from previously unstudied populations in Asia, South Africa, Europe, and the Americas could, in each case, transform Mtz(s) H. pylori to Mtz(r); (ii) Mtz(r) mutant derivatives of a cultured Mtz(s) strain resulted from mutation in rdxA; and (iii) transformation of Mtz(s) strains with rdxA-null alleles usually resulted in moderate level Mtz resistance (16 μg/ml). However, resistance to higher Mtz levels was common among clinical isolates, a result that implicates at least one additional gene. Expression in Escherichia coli of frxA (HP0642; flavin oxidoreductase), an rdxA paralog, made this normally resistant species Mtz(s), and frxA inactivation enhanced Mtz resistance in rdxA-deficient cells but had little effect on the Mtz susceptibility of rdxA + cells. Strains carrying frxA-null and rdxA-null alleles could mutate to even higher resistance, a result implicating one or more additional genes in residual Mtz susceptibility and hyperresistance. We conclude that most Mtz resistance in H. pylori depends on rdxA inactivation, that mutations in frxA can enhance resistance, and that genes that confer Mtz resistance without rdxA inactivation are rare or nonexistent in H. pylori populations.
Persistent Identifierhttp://hdl.handle.net/10722/49111
ISSN
2015 Impact Factor: 3.198
2015 SCImago Journal Rankings: 2.216
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorJeong, JYen_HK
dc.contributor.authorMukhopadhyay, AKen_HK
dc.contributor.authorDailidiene, Den_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorVelapatino, Ben_HK
dc.contributor.authorGilman, RHen_HK
dc.contributor.authorParkinson, AJen_HK
dc.contributor.authorNair, GBen_HK
dc.contributor.authorWong, BCYen_HK
dc.contributor.authorShiu Kum Lamen_HK
dc.contributor.authorMistry, Ren_HK
dc.contributor.authorSegal, Ien_HK
dc.contributor.authorYuan, Yen_HK
dc.contributor.authorGao, Hen_HK
dc.contributor.authorAlarcon, Ten_HK
dc.contributor.authorBrea, MLen_HK
dc.contributor.authorIto, Yen_HK
dc.contributor.authorKersulyte, Den_HK
dc.contributor.authorLee, HKen_HK
dc.contributor.authorGong, Yen_HK
dc.contributor.authorGoodwin, Aen_HK
dc.contributor.authorHoffman, PSen_HK
dc.contributor.authorBerg, DEen_HK
dc.date.accessioned2008-06-12T06:34:40Z-
dc.date.available2008-06-12T06:34:40Z-
dc.date.issued2000en_HK
dc.identifier.citationJournal Of Bacteriology, 2000, v. 182 n. 18, p. 5082-5090en_HK
dc.identifier.issn0021-9193en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49111-
dc.description.abstractHelicobacter pylori is a human-pathogenic bacterial species that is subdivided geographically, with different genotypes predominating in different parts of the world. Here we test and extend an earlier conclusion that metronidazole (Mtz) resistance is due to mutation in rdxA (HP0954), which encodes a nitroreductase that converts Mtz from prodrug to bactericidal agent. We found that (i) rdxA genes PCR amplified from 50 representative Mtz(r) strains from previously unstudied populations in Asia, South Africa, Europe, and the Americas could, in each case, transform Mtz(s) H. pylori to Mtz(r); (ii) Mtz(r) mutant derivatives of a cultured Mtz(s) strain resulted from mutation in rdxA; and (iii) transformation of Mtz(s) strains with rdxA-null alleles usually resulted in moderate level Mtz resistance (16 μg/ml). However, resistance to higher Mtz levels was common among clinical isolates, a result that implicates at least one additional gene. Expression in Escherichia coli of frxA (HP0642; flavin oxidoreductase), an rdxA paralog, made this normally resistant species Mtz(s), and frxA inactivation enhanced Mtz resistance in rdxA-deficient cells but had little effect on the Mtz susceptibility of rdxA + cells. Strains carrying frxA-null and rdxA-null alleles could mutate to even higher resistance, a result implicating one or more additional genes in residual Mtz susceptibility and hyperresistance. We conclude that most Mtz resistance in H. pylori depends on rdxA inactivation, that mutations in frxA can enhance resistance, and that genes that confer Mtz resistance without rdxA inactivation are rare or nonexistent in H. pylori populations.en_HK
dc.format.extent384 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Microbiology.en_HK
dc.relation.ispartofJournal of Bacteriologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsJournal of Bacteriology. Copyright © American Society for Microbiology.en_HK
dc.rightsCopyright © American Society for Microbiology, Journal of Bacteriology, 2000, v. 182 n. 18, p. 5082-5090en_HK
dc.subject.meshAnti-Bacterial Agents - pharmacologyen_HK
dc.subject.meshDrug Resistance, Microbial - geneticsen_HK
dc.subject.meshHelicobacter pylori - drug effects - enzymology - genetics - isolation & purificationen_HK
dc.subject.meshMetronidazole - pharmacologyen_HK
dc.subject.meshNitroreductases - genetics - metabolismen_HK
dc.titleSequential inactivation of rdxA (hp0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylorien_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9193&volume=182&issue=18&spage=5082&epage=5090&date=2000&atitle=Sequential+inactivation+of+rdxA+(HP0954)+and+frxA+(HP0642)+nitroreductase+genes+causes+moderate+and+high-level+metronidazole+resistance+in+Helicobacter+pylorien_HK
dc.identifier.emailWong, BCY:bcywong@hku.hken_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1128/JB.182.18.5082-5090.2000en_HK
dc.identifier.pmid10960091-
dc.identifier.pmcidPMC94655en_HK
dc.identifier.scopuseid_2-s2.0-0033811410en_HK
dc.identifier.hkuros62028-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033811410&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume182en_HK
dc.identifier.issue18en_HK
dc.identifier.spage5082en_HK
dc.identifier.epage5090en_HK
dc.identifier.isiWOS:000089055900008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridJeong, JY=7402045887en_HK
dc.identifier.scopusauthoridMukhopadhyay, AK=7201816905en_HK
dc.identifier.scopusauthoridDailidiene, D=6506309198en_HK
dc.identifier.scopusauthoridWang, Y=9747395700en_HK
dc.identifier.scopusauthoridVelapatino, B=6602471719en_HK
dc.identifier.scopusauthoridGilman, RH=36044231400en_HK
dc.identifier.scopusauthoridParkinson, AJ=7102534966en_HK
dc.identifier.scopusauthoridNair, GB=7201482255en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.scopusauthoridShiu Kum Lam=7409550162en_HK
dc.identifier.scopusauthoridMistry, R=7006377283en_HK
dc.identifier.scopusauthoridSegal, I=7103331239en_HK
dc.identifier.scopusauthoridYuan, Y=8922152900en_HK
dc.identifier.scopusauthoridGao, H=37020927100en_HK
dc.identifier.scopusauthoridAlarcon, T=7006664623en_HK
dc.identifier.scopusauthoridBrea, ML=24329222900en_HK
dc.identifier.scopusauthoridIto, Y=7410024219en_HK
dc.identifier.scopusauthoridKersulyte, D=6603724765en_HK
dc.identifier.scopusauthoridLee, HK=7501488409en_HK
dc.identifier.scopusauthoridGong, Y=55226942200en_HK
dc.identifier.scopusauthoridGoodwin, A=7102795899en_HK
dc.identifier.scopusauthoridHoffman, PS=7202878631en_HK
dc.identifier.scopusauthoridBerg, DE=7202401139en_HK

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