Analysis of Clinical Isolates of Helicobacter pylori in Pakistan Reveals High Degrees of Pathogenicity and High Frequencies of Antibiotic Resistance. Issue 5 (14th May 2014)

• Record Type: Journal Article
• Authors: Rasheed, Faisal; Campbell, Barry James; Alfizah, Hanafiah; Varro, Andrea; Zahra, Rabaab; Yamaoka, Yoshio; Pritchard, David Mark
• Is Part Of: Helicobacter. Volume 19:Issue 5(2014:Oct.)
• Page Start: 387
• Page End: 399
• Publication Date: 2014-05-14
• Subjects: Helicobacter -- Periodicals; Helicobacter infections -- Periodicals; Stomach -- Diseases -- Periodicals; 616.3301405
• DOI: 10.1111/hel.12142
• Languages: English
• ISSNs: 1083-4389

Abstract

<abstract abstract-type="main" id="hel12142-abs-0001"> <title>Abstract</title> <sec id="hel12142-sec-0001" sec-type="section"> <title>Background</title> <p>Antibiotic resistance in <italic>Helicobacter pylori</italic> contributes to failure in eradicating the infection and is most often due to point and missense mutations in a few key genes.</p> </sec> <sec id="hel12142-sec-0002" sec-type="section"> <title>Methods</title> <p>The antibiotic susceptibility profiles of <italic>H. pylori</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.</p> </sec> <sec id="hel12142-sec-0003" sec-type="section"> <title>Results</title> <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 = 43) exhibited resistance to one or more antibiotics. MTZ‐resistant isolates contained missense mutations in oxygen‐independent NADPH nitroreductase (RdxA; 8 mutations found) and NADH flavin oxidoreductase (FrxA; 4 mutations found). In the 23S <italic>rRNA</italic> gene, responsible for CLR resistance, a new point mutation (A2181G) and 4 previously reported mutations were identified. Pathogenicity genes <italic>cagA</italic>, <italic> dupA, </italic> and <italic>vacA</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′ region of <italic>cagA</italic> throughout the tree.</p> </sec> <sec id="hel12142-sec-0004" sec-type="section"> <title>Conclusions</title> <p>We have identified <italic>H. pylori</italic> isolates in Pakistan which harbor pathogenicity genes and worrying antibiotic resistance profiles as a result of having acquired multiple point and missense mutations. <italic>H. pylori</italic> eradication regimens should therefore be reevaluated in this setting.</p> </sec> </abstract>