Efflux pump mediated antibiotic resistance in clinical isolates of Helicobacter pylori from South West Nigeria.
Abstract
Introduction
Helicobacter pylori is a spiral shaped gram negative bacterium majorly causing peptic ulcers and gastric cancer in humans. The combinations of two or more antibiotics such as amoxicillin, clarithromycin, metronidazole or tetracycline with anti-secretory agents or bismuth have been used successfully for the treatment of H. pylori.
Aim
Increasing antibiotic resistance has been a contributory factor to treatment failures; as such evaluation of resistance mechanism will improve the management of H. pylori infection.
Methodology
The antibiotic resistance in H. pylori isolates from Nigeria was determined using E-test strips from Biomerieux SA, France and PCR for the efflux pump gene detection.
Results
Resistance to metronidazole was found to be 93% (97/104), amoxicillin 42% (44/104), clarithromycin 39% (41/104) and tetracycline 27% (28/104). However 51% (53/104) of the isolates harboured multidrug efflux pump gene hefA (Hp605) and 34% (35/104) hefD (Hp 971). However, hefG (Hp 1327) was absent in all the isolates. There was significant association between clarithromycin resistance and hefA with p-value 0.014, there was also association between amoxicillin resistance and hefD with p-value 0.004.
Conclusion
The present study revealed that H. pylori antibiotic resistance is on the increase in Nigerian strains and the mechanism of resistance may possibly include the possession of multidrug efflux pump.
Keywords
References
Marshal BJ. Helicobacter pylori: A Primer for 1994. Gastroenterol. 1993; 1: 241-247.
Blaser MJ. Hypotheses on the Pathogenesis and Natural History of Helicobacter pylori –induced Inflammation. Gastroenterol. 1992; 102: 720-727.
Graham DY. Antibiotic Resistance Helicobacter pylori of: Implications for Therapy. Gastroenterol. 1998; 115:1272-1277.
Graham DY. Therapy of Helicobacter pylori: Current Status and Issues. Gastroenterol. 2000; 118:52-58.
Graham DY, Shiotani A. New Concepts of Resistance in the Treatment of Helicobacter pylori Infections. Nat. Clin. Pract. Gastroenterol. Hepatol. 2008; 5: 321–331.
Meyer JM, Silliman NP, Wang W, Siepman NY, Sugg JE, Morris D, Zhang J, Bhattacharyya H, King EC, Hopkins RJ. Risk Factors for Helicobacter pylori Resistance in the United States: The Surveillance of H. pylori Antimicrobial Resistance Partnership (SHARP) Study, 1993‐1999. Ann. Intern. Med. 2002; 136: 13–24.
Jaka H, Rhee JA, Ostlundh L, Smart L, Peck R, Mueller A, Kasang C, Mshana S. The Magnitude of Antibiotic Resistance to Helicobacter pylori in Africa and Identified Mutations which Confer Resistance to Antibiotics: Systematic Review and Meta-analysis. BMC Infect. Dis. 2018; 18: 193.
Harrison U, Fowora MA, Seriki AT, Loell E, Mueller S, Ugo‒Ijeh M, Onyekwere CA, Lesi OA, Otegbayo JA, Akere A, Ndububa DA, Adekanle O, Anomneze E, Abdulkareem FB, Adeleye IA, Crispin A, Rieder G, Fischer W, Smith SI and Haas R. Helicobacter pylori Strains from A Nigerian Cohort Show Divergent Antibiotic Resistance Rates and A Uniform Pathogenic Profile. PloS One 2017; 12 (5): e0176454.
Qureshi NN, Gallaher B, Schiller NL. Evolution of Amoxicillin Resistance of Helicobacter pylori in vitro: Characterization of Resistance Mechanisms. Micro. Drug. Resist. 2014; 20 (6): 509-516.
Jacoby GA, Schiller NL. New Mechanisms of Bacteria Resistance to Antimicrobial Agents. N. Engl. J. Med 1991; 324:601-612.
Livermore DM. ß-lactamases in Laboratory and Clinical Resistance. Clinic. Microbiol. Rev. 1995; 8: 557-584.
Goffin C, Ghuysen JM. Multimodular Penicillin-binding Proteins: An Enigmatic Family of Orthologs and Paralogs. Microbiol. Mol. Biol. Revi. 1998; 62: 1079-1093.
Gerrits MM, Godoy APO, Kuipers EJ, Ribeiro ML. Multiple Mutations in or Adjacent to the Conserved Penicillin-binding Protein Motifs of the Penicillin-binding Protein 1A Confer Amoxicillin Resistance to Helicobacter pylori. Helicobacter 2006; 11 (3): 181-187.
Dore MP, Kwon DH, Sepulveda AR, El-Zimaity H, Yamaoka Y, Osato MS, Mototsugu K, Nieddu AM, Realdi G. Graham DY. Isolation of Helicobacter pylori from Sheep: Implications for Transmission to Humans. Am. J. Gastroenterol. 2001; 96: 1396-1401.
Nikaido H. Structure and Mechanism of RND-type Multidrug Efflux Pumps. Adv. Enzymol. Relat. Areas Mol. Biol. 2011; 77: 1–60.
Westblom TU, Madan E, Riff BR. Improved growth of H. pylori using a Liquid Medium Supplemented with Human Serum. Ital. J. Gastroenterol. 1991. 29 (2):48.
Ahmad N, Zakaria WR, Mohamed R. Analysis of Antibiotic Susceptibility Patterns of Helicobacter pylori Isolates from Malaysia. Helicobacter 2011; 16: 47-51.
Liu Z, Zheng P, Yang P. Efflux Pump Gene hefA of Helicobacter pylori Plays an Important Role in Multidrug Resistance. World J. Gastroenterol. 2008; 14 (33): 5217-5222.
Mendonca S, Ecclissato C, Sartori SM, Godoy AP, Guerzoni RA, Degger M, Pedrazzoli J. Prevalence of Helicobacter pylori Resistance to Metronidazole, Clarithromycin, Amoxicillin, Tetracycline and Furazolidone in Brazil. Helicobacter 2000; 5 (2): 79-83.
Ghotaslou R, Leylabadlo HE, Asl YM. Prevalence of Antibiotic Resistance in Helicobacrter pylori: A Recent Literature Review. World J. Methodol. 2015; 5 (3): 164-174.
Bina JE, Alm RA, Uria-Nickelsen M, Thomas SR, Trust TJ, Hancock RE. Helicobacter pylori Uptake and Efflux: Basis for Intrinsic Susceptibility to Antibiotics in vitro. Antimicrob. Agents. Chemother. 2000. 44:248-254.
Kutschke A, de Jonge BL. Compound Efflux in Helicobacter pylori. Antimicrob. Agents. Chemother. 2005. 49:3009-3010.
Huang YQ, Huang GR, Wu MH, Tang HY, Hung ZS, Zhou XH, Yu WQ, Su JW, Mo XQ, Chen BP, Zhao LJ, Huang XF, Wei HY, Wei LD. Inhibitory Effects of Emodin, baicalin, Schizandrin and Berberine on hefA genes: Treatment of Helicobacter pylori-induced Multidrug Resistance. World J. gastroenterol. 2015; 21: 4225-4231.
Amsterdam KV, Bart A, Ende AVD. A Helicobacter pylori Tolc Efflux Pump Confers Resistance to Metronidazole. Antimicrob. Agents Chemother. 2005; 49 (4):1477-1482.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution 3.0 License.