Analysis of Clinical Isolates of <i>Helicobacter pylori</i> in Pakistan Reveals High Degrees of Pathogenicity and High Frequencies of Antibiotic Resistance

Rasheed, Faisal; Campbell, Barry J.; Hanafiah, Alfizah; Varró, Andrea; Zahra, Rabaab; Yamaoka, Yoshio; Pritchard, D. Mark

doi:10.1111/hel.12142

Cited by 59 publications

(53 citation statements)

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“…AMX is one of the most commonly used antibiotics in recent years in Nepal as similar as ceftriaxone and gentamycin [36]. Additionally we observed no resistance to TCN, in contrast to studies from India and Pakistan [22, 32, 35, 37]. TCN is used as a salvage quadruple therapy [28, 38] and may be a useful alternative first-line regimen in Nepal.…”

Section: Discussionmentioning

confidence: 49%

“…Together with CAM or MNZ, AMX is the first-line regimen for treatment of H. pylori infection particularly as a secondary antibiotic in the low efficacy of CAM-based triple treatment zone [28–31]. Although in general the AMX resistance is rare, the increasing AMX primary resistance rates have been reported in the neighbor’s country; India and Pakistan [22, 32–35]. AMX is one of the most commonly used antibiotics in recent years in Nepal as similar as ceftriaxone and gentamycin [36].…”

Section: Discussionmentioning

confidence: 99%

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Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal

et al. 2016

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BackgroundThe prevalence of Helicobacter pylori antibiotic susceptibility in the Nepalese strains is untracked. We determined the antibiotic susceptibility for H. pylori and analyzed the presence of genetic mutations associated with antibiotic resistance in Nepalese strains.ResultsThis study included 146 consecutive patients who underwent gastroduodenal endoscopy in Kathmandu, Nepal. Among 42 isolated H. pylori, there was no resistance to amoxicillin and tetracycline. In contrast, similar with typical South Asian patterns; metronidazole resistance rate in Nepalese strains were extremely high (88.1 %, 37/42). Clarithromycin resistance rate in Nepalese strains were modestly high (21.4 %, 9/42). Most of metronidazole resistant strains had highly distributed rdxA and frxA mutations, but were relative coincidence without a synergistic effect to increase the minimum inhibitory concentration (MIC). Among strains with the high MIC, 63.6 % (7/11) were associated with frameshift mutation at position 18 of frxA with or without rdxA involvement. However, based on next generation sequencing data we found that one strain with the highest MIC value had a novel mutation in the form of amino acid substituted at Ala-212, Gln-382, Ile-485 of dppA and Leu-145, Thr-168, Glu-117, Val-121, Arg-221 in dapF aside from missense mutations in full-length rdxA. Mutations at Asn-87 and/or Asp-91 of the gyrA were predominantly in levofloxacin-resistant strains. The gyrB mutation had steady relationship with the gyrA 87–91 mutations. Although three (44.4 %) and two (22.2 %) of clarithromycin resistant strains had point mutation on A2143G and A2146G, we confirmed the involvement of rpl22 and infB in high MIC strains without an 23SrRNA mutation.ConclusionsThe rates of resistance to clarithromycin, metronidazole and levofloxacin were high in Nepalese strains, indicating that these antibiotics-based triple therapies are not useful as first-line treatment in Nepal. Bismuth or non-bismuth-based quadruple regimens, furazolidone-based triple therapy or rifabutin-based triple therapy may become alternative strategy in Nepal.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0873-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal

et al. 2016

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“…Our study demonstrated the distribution of rdxA and frxA mutation sites was random, scattered, and irregular. 39,41 Additionally, some antibiotic-resistant strains have no rdxA mutation, suggesting other resistant mechanisms such as mutation of ferric uptake regulator, overexpression of a DNA repair protein, tolC efflux pump, or Lon protease may also relate with the acquisition of MNZ resistance in H. pylori, [42][43][44][45] which needs further investigation. Molecular docking studies showed there were some sites of those four types relevant with resistant after mutation, for example, 33 and 35 sites of the first type; 58 and 192 of the second type; S45N and Y47C of the third type; M21V/I/A, A118S, and K64N of the forth type.…”

Section: Discussionmentioning

confidence: 99%

Molecular detection of H. pylori antibiotic‐resistant genes and molecular docking analysis

et al. 2019

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To explore the mutation characteristics of H. pylori resistance-related genes to antibiotics of clarithromycin (CAM), levofloxacin (LVX) and metronidazole, 23SrRNA, gyrA, gyrB, rdxA, and frxA genes were amplified and sequenced, respectively. Molecular docking study was performed to explore molecular interactions between chemotherapeutic agents and target proteins. In the CAM-resistant strains, the mutation rate in site A2143G was 74.2% (n = 23). The interactions in sites of G1949A, C1953T, and G2211T with CAM were weaker after mutation. In the LVX-resistant strains, the mutation rates in 87 (N to K/I) and 91 (D to N/Y/G) of gyrA were 28.6% (n = 16) and 12.5% (n = 7), respectively. We could infer by docking studies that N87 K/I, D91Y/G/N, D99N, and D143E mutations in GyrA protein all had weakened interaction with LVX. The mutation types of RdxA protein consisted of protein truncation caused by premature stop codons (n = 26, 33.3%), frameshift mutations (n = 8, 10.3%), FMN-binding sites (n = 16, 20.5%), and the others (n = 11, 14.1%).Docking analysis showed that some mutations in those four types of RdxA protein could reduce interaction with MNZ, and play a significant role in antibiotic resistance. What's more, we performed natural transformation with some of these mutated DNA fragments to see if they really impact susceptibility to antibiotics. Our study suggested that in addition to the reported mutation sites, H. pylori antibiotic resistance in this region may also be associated with changes in some new sites. Our study provides novel ideas and methods for the identification of H. pylori resistancerelated mutations, and also clues and basis for further investigation on specific molecular mechanism.

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“…In H. pylori strains recently isolated from biopsies of 46 patients, 37 (80.4%) of the 46 H. pylori clinical isolates were positive for cagA [40]. Additionally, the cagA gene was mostly accompanied by vacA s1m1 genotype in these isolates.…”

Section: Discussionmentioning

confidence: 94%

Prevalence of H. pylori in gastric biopsy specimen in the southeastern region of Turkey

Bilman¹,

Özdemir

Baysal

et al. 2016

J Infect Dev Ctries

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Introduction: Helicobacter pylori is a Gram-negative, microaerophilic bacterium that colonizes human gastric mucosa. Gastric ulcer, duodenal ulcer, chronic atrophic gastritis, mucosa-associated lymphoid tissue lymphoma, and stomach adenocarcinoma are associated with H. pylori as the etiological agent. Cytotoxin-associated gene A (cagA), which is one of the most important virulence factors of H. pylori, encodes a 120-145 kDa protein.The prevalence of cagA genes shows differences in H. pylori infections based on geographical area, and cagA-positive H. pylori strains play an important role in pathogenesis of gastric carcinoma. Methodology: The aim of this study was to detect the prevalence of cagA and vacA genes in H. pylori isolates in adult patient groups in the southeastern region of Turkey. The presence of H. pylori was investigated in gastric biopsy specimens using the culture method, and polymerase chain reaction (PCR) analysis was performed to detect the presence of the cagA and vacA s1 genes. Results: H. pylori was detected in 65% (84/129) of patients who had gastrointestinal complaints. The number of vacA s1 and cagA genes of isolates were 44 (74.5%) and 31 (52.5%), respectively. Conclusions: H. pylori infection in southeastern region of Turkey with are comparable to those in developed countries. Patients with cagA-and vacA-positive H. pylori have a higher risk of severe inflammation and atrophy and should therefore be monitored for the development of gastric cancer.

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Analysis of Clinical Isolates of Helicobacter pylori in Pakistan Reveals High Degrees of Pathogenicity and High Frequencies of Antibiotic Resistance

Cited by 59 publications

References 71 publications

Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal

Emerging Helicobacter pylori levofloxacin resistance and novel genetic mutation in Nepal

Molecular detection of H. pylori antibiotic‐resistant genes and molecular docking analysis

Prevalence of H. pylori in gastric biopsy specimen in the southeastern region of Turkey

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