DOI QR코드

DOI QR Code

Identification of a Novel Cassette Array in Integron-bearing Helicobacter Pylori Strains Isolated from Iranian Patients

  • Goudarzi, Mehdi (Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences) ;
  • Seyedjavadi, Sima Sadat (Department of Medical Mycology, Pasteur institute of Iran) ;
  • Fazeli, Maryam (WHO collaborating center for reference and research on rabies, Pasteur Institute of Iran) ;
  • Roshani, Maryam (Department of Biology, Faculty of Science, University Putra Malaysia) ;
  • Azad, Mehdi (Department of Medical Laboratory Sciences, School of Paramedicine, Qazvin University of Medical Sciences) ;
  • Heidary, Mohsen (Department of Medical Microbiology, Faculty of Medicine, Iran University of Medical Sciences) ;
  • Navidinia, Masoumeh (Department of Medical Laboratory Sciences, School of Paramedicine, Shahid Beheshti University of Medical Science) ;
  • Goudarzi, Hossein (Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences)
  • Published : 2016.07.01

Abstract

Helicobacter pylori as the second most common cause of gastric cancer in the world infects approximately half of the developed countries population and 80% of the population living in developing countries. Integrons as genetic reservoirs play major roles in dissemination of antimicrobial resistance genes. To the best of our knowledge, this is the first study to report carriage of class 1 and 2 integrons and associated gene cassettes in H. pylori isolates from Iran. This cross-sectional study was conducted in Tehran among 110 patients with H. pylori infection. Antimicrobial susceptibility testing (AST) for H. pylori strains were assessed by the micro broth dilution method. Class 1 and 2 integrons were detected using PCR. In order to determine gene cassettes, amplified fragments were subjected to DNA sequencing of both amplicon strands. The prevalence of resistance to clarithromycin, metronidazole, clarithromycin, tetracycline, amoxicillin, rifampin, and levofloxacin were 68.2% (n=75), 25.5% (n=28), 24.5% (n=27), 19.1% (n=21), 18.2% (n=20) and 16.4% (n=18), respectively. Frequency of multidrug resistance among H. pylori isolates was 12.7%. Class 2 integron was detected in 50 (45.5%) and class 1 integron in 10 (9.1%) H. pylori isolates. The most predominant gene cassette arrays in class 2 integron-bearing H. pylori were included sat-era-aadA1, dfrA1-sat2-aadA1, blaoxa2 and, aadB whereas common gene cassette arrays in class 1 integron were aadB-aadA1-cmlA6, aacA4, blaoxa2, and catB3. The high frequency of class 2 integron and multidrug resistance in the present study should be considered as a warning for clinicians that continuous surveillance is necessary to prevent the further spread of resistant isolates.

Keywords

H. pylori;integron s;multidrug-resistant strains;Iran

Acknowledgement

Supported by : Shahid Beheshti University of Medical Sciences

References

  1. Aboderin OA, Abdu A, Odetoyin BW, et al (2007). Antibiotic resistance of Helicobacter pylori from patients in Ile-Ife, South-west, Nigeria. Afr Health Sci, 7, 143-7.
  2. Ahmed KS, Ghebremedhin AA, Khan AA, et al (2012). determination of antibiotic sensitivity pattern of Helicobacter pylori Isolates from South India Population. Adv Microbiol, 2, 263. https://doi.org/10.4236/aim.2012.23031
  3. Asaka M, Kato M, Takahashi Si, et al (2010). Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter, 15, 1-20.
  4. Boyanova L, Evstatiev I, Gergova G, et al (2015). Linezolid susceptibility in Helicobacter pylori, including strains with multidrug resistance. Int J Antimicrob Agent, 46, 703-6. https://doi.org/10.1016/j.ijantimicag.2015.08.010
  5. Boyanova L, Koumanova R, Gergova G, et al (2002). Prevalence of resistant Helicobacter pylori isolates in Bulgarian children. J Med Microbiol, 51, 786-90. https://doi.org/10.1099/0022-1317-51-9-786
  6. Caliskan R, Tokman HB, Erzin Y, et al (2015). Antimicrobial resistance of Helicobacter pylori strains to five antibiotics, including levofloxacin, in Northwestern Turkey. Rev Soc Bras Med Trop, 48, 278-84. https://doi.org/10.1590/0037-8682-0027-2015
  7. Cambray G, Guerout A-M, Mazel D (2010). Integrons. Annu Rev Genet, 44, 141-66. https://doi.org/10.1146/annurev-genet-102209-163504
  8. Chung JW, Lee GH, Jeong JY, et al (2012). Resistance of Helicobacter pylori strains to antibiotics in Korea with a focus on fluoroquinolone resistance. J Gastroenterol Hepatol, 27, 493-7. https://doi.org/10.1111/j.1440-1746.2011.06874.x
  9. Correa P, Piazuelo MB (2008). Natural history of Helicobacter pylori infection. Dig Liver Dis, 40, 490-6. https://doi.org/10.1016/j.dld.2008.02.035
  10. Crespo O, Catalano M, Pineiro S, et al (2005). Tn7 distribution in Helicobacter pylori: a selective paradox. Int J Antimicrob Agents, 25, 341-4. https://doi.org/10.1016/j.ijantimicag.2005.01.016
  11. De Francesco V, Margiotta M, Zullo A, et al (2006). Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med, 144, 94-100. https://doi.org/10.7326/0003-4819-144-2-200601170-00006
  12. Fathi MS, EL-Folly RF, Hassan RA, et al (2013). Genotypic and phenotypic patterns of antimicrobial susceptibility of Helicobacter pylori strains among Egyptian patients. Egypt J Med Hum Genet, 14, 235-46. https://doi.org/10.1016/j.ejmhg.2013.03.004
  13. Fuccio L, Zagari RM, Eusebi LH, et al (2009). Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med, 151, 121-8. https://doi.org/10.7326/0003-4819-151-2-200907210-00009
  14. Gillings MR (2014). Integrons: past, present, and future. Microbiol Mol Biol Rev, 78, 257-77. https://doi.org/10.1128/MMBR.00056-13
  15. Godoy AP, Ribeiro ML, Benvengo YH, et al (2003). Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates. BMC gastroenterol, 3, 20. https://doi.org/10.1186/1471-230X-3-20
  16. Goudarzi H, Seyedjavadi SS, Fazeli M, et al (2015). Genotyping of Peroxisome Proliferator-Activated Receptor gamma in Iranian Patients with Helicobacter pylori Infection. Asian Pac J Cancer Prev, 16, 5219-23. https://doi.org/10.7314/APJCP.2015.16.13.5219
  17. Hu CT, Wu CC, Lin CY, et al (2007). Resistance rate to antibiotics of Helicobacter pylori isolates in eastern Taiwan. J Gastroenterol Hepato, 22, 720-3.
  18. John Albert M, Al-mekhaizeem K, Neil L, et al (2006). High prevalence and level of resistance to metronidazole, but lack of resistance to other antimicrobials in Helicobacter pylori, isolated from a multiracial population in Kuwait. Aliment Pharmacol Ther, 24, 1359-66. https://doi.org/10.1111/j.1365-2036.2006.03144.x
  19. Kim N, Kim JM, Kim CH, et al (2006). Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea. J Clin Gastroenterol, 40, 683-7. https://doi.org/10.1097/00004836-200609000-00004
  20. Kobayashi I, Murakami K, Kato M, et al (2007). Changing antimicrobial susceptibility epidemiology of Helicobacter pylori strains in Japan between 2002 and 2005. J Clin Microbiol, 45, 4006-10. https://doi.org/10.1128/JCM.00740-07
  21. Loffeld R, Werdmuller B (2013). Changes in antibiotic susceptibility of Helicobacter pylori in the course of eight years in the Zaanstreek region in the Netherlands. Gastroent Res Pract, 2013.
  22. Malfertheiner P, Megraud F, O'Morain CA, et al (2012). Management of Helicobacter pylori infection-the Maastricht IV/Florence consensus report. Gut, 61, 646-64. https://doi.org/10.1136/gutjnl-2012-302084
  23. Manfredi M, Gismondi P, Maffini V, et al (2015). Primary antimicrobial susceptibility changes in children with helicobacter pylori infection over 13 years in Northern Italy. Gastroent Res Pract, 2015.
  24. Masaoka T, Suzuki H, Kurabayashi K, et al (2006). Could frameshift mutations in the frxA and rdxA genes of Helicobacter pylori be a marker for metronidazole resistance? Aliment Pharmacol Ther, 24, 81-7. https://doi.org/10.1111/j.1365-2036.2006.02969.x
  25. Milani M, Ghotaslou R, Akhi MT, et al (2012). The status of antimicrobial resistance of Helicobacter pylori in Eastern Azerbaijan, Iran: comparative study according to demographics. J Infect Chemother, 18, 848-52. https://doi.org/10.1007/s10156-012-0425-4
  26. Moura A, Henriques I, Ribeiro R, et al (2007). Prevalence and characterization of integrons from bacteria isolated from a slaughterhouse wastewater treatment plant. J Antimicrob Chemother, 60, 1243-50. https://doi.org/10.1093/jac/dkm340
  27. Ndip RN, Malange Takang AE, Ojongokpoko JE, et al (2008). Helicobacter pylori isolates recovered from gastric biopsies of patients with gastro-duodenal pathologies in Cameroon: current status of antibiogram. Trop Med Int Health, 13, 848-54. https://doi.org/10.1111/j.1365-3156.2008.02062.x
  28. Nishizawa T, Suzuki H (2014). Mechanisms of Helicobacter pylori antibiotic resistance and molecular testing. Front Mol Biosci, 1, 1-7.
  29. Ogata SK, Gales AC, Kawakami E (2014). Antimicrobial susceptibility testing for Helicobacter pylori isolates from Brazilian children and adolescents: comparing agar dilution, E-test, and disk diffusion. Braz J Microbiol, 45, 1439-48. https://doi.org/10.1590/S1517-83822014000400039
  30. Parsons H, Carter M, Sanders D, et al (2001). Helicobacter pylori antimicrobial resistance in the United Kingdom: the effect of age, sex and socio-economic status. Aliment Pharmacol Ther, 15, 1473-8. https://doi.org/10.1046/j.1365-2036.2001.01068.x
  31. Rafeey M, Ghotaslou R, Nikvash S, et al (2007). Primary resistance in Helicobacter pylori isolated in children from Iran. J Infec Chemother, 13, 291-5. https://doi.org/10.1007/s10156-007-0543-6
  32. Seck A, Mbengue M, Gassama-Sow A, et al (2009). Antibiotic susceptibility of Helicobacter pylori isolates in Dakar, Senegal. J Infect Dev Countr, 3, 137-40.
  33. Sherif M, Mohran Z, Fathy H, et al (2004). Universal high-level primary metronidazole resistance in Helicobacter pylori isolated from children in Egypt. J Clin Microbiol, 42, 4832-4. https://doi.org/10.1128/JCM.42.10.4832-4834.2004
  34. Smith SM, O'Morain C, McNamara D (2014). Antimicrobial susceptibility testing for Helicobacter pylori in times of increasing antibiotic resistance. World J Gastroenterol, 20, 9912-21. https://doi.org/10.3748/wjg.v20.i29.9912
  35. Wu H, Shi X, Wang H, et al (2000). Resistance of Helicobacter pylori to metronidazole, tetracycline and amoxycillin. J Antimicrob Chemother, 46, 121-3. https://doi.org/10.1093/jac/46.1.121
  36. Wueppenhorst N1, Stueger HP, Kist M, Glocker EO (2013). High secondary resistance to quinolones in German Helicobacter pylori clinical isolates. J Antimicrob Chemother, 68, 1562-6. https://doi.org/10.1093/jac/dkt061
  37. Yue JY, Yue J, Wang MY, et al (2014). CagA status & genetic characterization of metronidazole resistant strains of H. pylori from: A region at high risk of gastric cancer. Pak J Med Sci, 30, 804.