{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T15:17:16Z","timestamp":1769008636984,"version":"3.49.0"},"reference-count":72,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T00:00:00Z","timestamp":1400025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Higher Education Commission (Pakistan)","award":["117-3838-BM7-017"],"award-info":[{"award-number":["117-3838-BM7-017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Antibiotic resistance in <jats:italic>Helicobacter pylori<\/jats:italic> contributes to failure in eradicating the infection and is most often due to point and missense mutations in a few key genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The antibiotic susceptibility profiles of <jats:italic>H.\u00a0pylori<\/jats:italic> isolates from 46 Pakistani patients were determined by Etest. Resistance and pathogenicity genes were amplified, and sequences were analyzed to determine the presence of mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A high percentage of isolates (73.9%) were resistant to metronidazole (MTZ), with considerable resistance to clarithromycin (CLR; 47.8%) and amoxicillin (AML; 54.3%) also observed. Relatively few isolates were resistant to tetracycline (TET; 4.3%) or to ciprofloxacin (CIP; 13%). However, most isolates (n\u00a0=\u00a043) exhibited resistance to one or more antibiotics. MTZ\u2010resistant isolates contained missense mutations in oxygen\u2010independent NADPH nitroreductase (RdxA; 8 mutations found) and NADH flavin oxidoreductase (FrxA; 4 mutations found). In the 23S <jats:italic><jats:styled-content style=\"fixed-case\">rRNA<\/jats:styled-content><\/jats:italic> gene, responsible for CLR resistance, a new point mutation (A2181G) and 4 previously reported mutations were identified. Pathogenicity genes <jats:italic>cagA<\/jats:italic>,<jats:italic> dupA,<\/jats:italic> and <jats:italic>vacA<\/jats:italic> s1a\/m1 were detected frequently in isolates which were also found to be resistant to MTZ, CLR, and AML. A high percentage of CagA and VacA seropositivity was also observed in these patients. Phylogenetic analysis of partial sequences showed uniform distribution of the 3\u2032 region of <jats:italic>cagA<\/jats:italic> throughout the tree.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We have identified <jats:italic>H.\u00a0pylori<\/jats:italic> isolates in Pakistan which harbor pathogenicity genes and worrying antibiotic resistance profiles as a result of having acquired multiple point and missense mutations. <jats:italic>H.\u00a0pylori<\/jats:italic> eradication regimens should therefore be reevaluated in this setting.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.12142","type":"journal-article","created":{"date-parts":[[2014,5,15]],"date-time":"2014-05-15T02:47:17Z","timestamp":1400122037000},"page":"387-399","source":"Crossref","is-referenced-by-count":49,"title":["Analysis of Clinical Isolates of <i>Helicobacter pylori<\/i> in Pakistan Reveals High Degrees of Pathogenicity and High Frequencies of Antibiotic Resistance"],"prefix":"10.1111","volume":"19","author":[{"given":"Faisal","family":"Rasheed","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Institute of Translational Medicine University of Liverpool Liverpool L69 3GE UK"},{"name":"Department of Microbiology Quaid\u2010i\u2010Azam University Islamabad 45320 Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry James","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Institute of Translational Medicine University of Liverpool Liverpool L69 3GE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanafiah","family":"Alfizah","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology Faculty of Medicine Universiti Kebangsaan Malaysia Medical Centre 56000 Cheras Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Varro","sequence":"additional","affiliation":[{"name":"Department of Cellular &amp; Molecular Physiology Institute of Translational Medicine University of Liverpool Liverpool L69 3GE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabaab","family":"Zahra","sequence":"additional","affiliation":[{"name":"Department of Microbiology Quaid\u2010i\u2010Azam University Islamabad 45320 Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Department of Environmental and Preventive Medicine Oita University Faculty of Medicine Yufu 870\u20101192 Japan"},{"name":"Department of Medicine\u2010Gastroenterology Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine Houston TX 77030 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Mark","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Institute of Translational Medicine University of Liverpool Liverpool L69 3GE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1172\/JCI20925","article-title":"Helicobacter pylori persistence: biology and disease","volume":"11","author":"Blaser MJ","year":"2004","journal-title":"J Clin Invest"},{"key":"e_1_2_6_3_1","first-page":"386","article-title":"Primary and acquired Helicobacter pylori resistance to clarithromycin, metronidazole and amoxicillin\u2013influence on treatment outcome","volume":"93","author":"Adamek RJ","year":"1998","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100960100611"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.18.5082-5090.2000"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00806.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-2-11"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.2.477"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2006.00398.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.3.962-965.2001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46824-0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.3.976-980.2003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70365-8"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.7.927"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.01.009"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2009.05876.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.8.2258-2263.1998"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1999.0029900342"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.10.135"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007736"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222375399"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/09674845.2009.11730260"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199610000-00001"},{"key":"e_1_2_6_24_1","volume-title":"Helicobacter pylori Protocols (Methods in Molecular Medicine)","author":"Christopher LC","year":"1997"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026658301825"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0923-2508(03)00030-5"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00188-11"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp457"},{"key":"e_1_2_6_29_1","first-page":"167","article-title":"High frequency of cagA and vacA s1a\/m2 genotype among Helicobacter pylori infected gastric biopsies of Pakistani children","volume":"7","author":"Rasheed F","year":"2011","journal-title":"Mal J Microbiol"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.32.12.1461"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/12.Supplement_1.S107"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.3161"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.7.2169-2178.2003"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02166.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2010.00774.x"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2013.10.001"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i18.2245"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/09674845.2010.11730319"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-13-33"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70100-3"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(02)02405-8"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12020"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.17.5155-5162.2001"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.18.5091-5096.2000"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2008.00492.x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-9-87"},{"key":"e_1_2_6_47_1","first-page":"514","article-title":"Virulence attributes of Helicobacter pylori isolates & their association with gastroduodenal disease","volume":"133","author":"Saxena A","year":"2011","journal-title":"Indian J Med Res"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2009.00690.x"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2005.02.001"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-5378.1998.08056.x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2005.03783.x"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/356217"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.7.2274-2279.1999"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(03)00034-8"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-011-0631-6"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2007.03.012"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2001.16.5.579"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.39.7.2463-2465.2001"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.47776-0"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2007.00557.x"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230X-8-49"},{"key":"e_1_2_6_62_1","first-page":"333","article-title":"Cytotoxin genes of Helicobacter pylori in gastroduodenal disease patients of Karachi","volume":"18","author":"Hanif M","year":"2010","journal-title":"As Pac J Mol Biol Biotechnol"},{"key":"e_1_2_6_63_1","first-page":"460","article-title":"Dominant cagA\/vacA genotypes and coinfection frequency of H. pylori in peptic ulcer or chronic gastritis patients in Zhejiang Province and correlations among different genotypes, coinfection and severity of the diseases","volume":"20","author":"Chen XJ","year":"2005","journal-title":"Chin Med J (Engl)"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.8.3906-3916.2005"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.30.17771"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70223-3"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2007.00539.x"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2012.00956.x"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04095.x"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2011.06652.x"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02612.x"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.43.2.182"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-5378.2001.00019.x"}],"container-title":["Helicobacter"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhel.12142","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hel.12142","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T05:47:12Z","timestamp":1696312032000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hel.12142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,14]]},"references-count":72,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1111\/hel.12142"],"URL":"https:\/\/doi.org\/10.1111\/hel.12142","archive":["Portico"],"relation":{},"ISSN":["1083-4389","1523-5378"],"issn-type":[{"value":"1083-4389","type":"print"},{"value":"1523-5378","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,14]]}}}