Frequency of Helicobacter pylori nitroreductase RdxA mutations for metronidazole activation in a population in the Cauca Department, Colombia

Claudia Patricia Acosta, Andrés Javier Quiroga, Carlos H. Sierra, Alba Alicia Trespalacios, .

Keywords: Helicobacter pylori, mutations, nitroreductases, metronidazole, Colombia

Abstract

Introduction: Resistance to metronidazole is a key factor associated with Helicobacter pylori treatment failure. Even though resistance is mostly associated with RdxA nitroreductase mutations, studies of this H. pylori protein in Popayán (Colombia) are still incipient.
Objective: To evaluate the frequency of mutations in the RdxA nitroreductase in a population of patients with H. pylori-positive gastrointestinal disease.
Materials and methods: We amplified the DNA of 170 gastric biopsies by PCR to detect mutations in the RdxA nitroreductase. An analysis of DNA sequences translated into amino acid sequences was done and then compared to the reference strain 26695.
Results: The frequency of RdxA nitroreductase mutations in this study population was 78%. Its most frequent distribution was found in positions D59N (153 samples), R131K (101 samples), R90K (97 samples), A118T (42 samples), I160F (32 samples) and H97T (26 samples), and meaningful stop codons Q50*, D59*; E75*, C159* and I160* in five, one, three, ten and six samples, respectively. The most common virulence genotype was vacAs1/m1 cagA negative (48.6 %).
Conclusions: The high frequency of RdxA nitroreductase mutations in H. pylori isolates in Popayán (Colombia) indicates that empirical therapy with metronidazole may not be a valid option for the eradication of H. pylori in patients of the studied population.

Downloads

Download data is not yet available.
  • Claudia Patricia Acosta Grupo de Investigación en Genética Humana Aplicada, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Colombia Fundación InnovaGen, Popayán, Colombia
  • Andrés Javier Quiroga Grupo de Investigación en Genética Humana Aplicada, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Colombia Fundación InnovaGen, Popayán, Colombia
  • Carlos H. Sierra Grupo de Investigación en Genética Humana Aplicada, Facultad de Ciencias de la Salud, Universidad del Cauca, Popayán, Colombia Fundación InnovaGen, Popayán, Colombia
  • Alba Alicia Trespalacios Grupo de Enfermedades Infecciosas, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia

References

Martínez-Júlvez M, Rojas AL, Olekhnovich I, Angarica VE, Hoffman PS, Sancho J. Structure of RdxA–an oxygeninsensitive nitroreductase essential for metronidazole activation in Helicobacter pylori. FEBS J. 2012;279:4306-17. http://dx.doi.org/10.1111/febs.12020

Gatta L, Vakil N, Vaira D. Treatment of Helicobacter pylori in Latin America. Lancet. 2012;379:407-8. http://dx.doi.org/10.1016/S0140-6736(12)60181-0

Graham DY. Helicobacter pylori infection in the pathogenesis of duodenal ulcer and gastric cancer: A model. Gastroenterol. 1997;113:1983-91. http://dx.doi.org/10.1016/S0016-5085(97)70019-2

Mendz GL, Mégraud F. Is the molecular basis of metronidazole resistance in microaerophilic organisms understood? Trends Microbiol. 2002;10:370-5. http://dx.doi.org/10.1016/S0966-842X(02)02405-8

Gerrits MM, van Vliet AH, Kuipers EJ, Kusters JG. Helicobacter pylori and antimicrobial resistance: Molecular mechanisms and clinical implications. Lancet Infect Dis. 2006;6:699-709. http://dx.doi.org/10.1016/S1473-3099(06)70627-2

Kaakoush NO, Asencio C, Mégraud F, Mendz GL. A redox basis for metronidazole resistance in Helicobacter pylori. Antimicrob Agents Chemother. 2009;53:1884-91. http://dx.doi.org/10.1128/AAC.01449-08

Camargo MC, García A, Riquelme A, Otero W, Camargo CA, Hernández-García T, et al. The problem of Helicobacter pylori resistance to antibiotics: A systematic review in Latin America. Am J Gastroenterol. 2014;109:485-95. http://dx.doi.org/10.1038/ajg.2014.24

Martínez M, David J, Henao R, Consuelo S, Lizarazo R, Iván J. Resistencia antibiótica del Helicobacter pylori en América Latina y el Caribe. Rev Colomb Gastroenterol. 2014;29:218-27.

Aldana LP, Kato M, Kondo T, Nakagawa S, Zheng R, Sugiyama T, et al. In vitro induction of resistance to metronidazole, and analysis of mutations in rdxA and frxA genes from Helicobacter pylori isolates. J Infect Chemother. 2005;11:59-63. http://dx.doi.org/10.1007/s10156-004-0370

Mirzaei N, Poursina F, Moghim S, Rahimi E, Safaei HG. The mutation of the rdxA gene in metronidazole-resistant Helicobacter pylori clinical isolates. Adv Biomed Res. 2014;3:90. http://dx.doi.org/10.4103/2277-9175.128469

Marais A, Bilardi C, Cantet F, Mendz GL, Mégraud F. Characterization of the genes rdxA and frxA involved in metronidazole resistance in Helicobacter pylori. Res

Microbiol. 2003;154:137-44. http://dx.doi.org/10.1016/S0923-2508(03)00030-5

Jenks P, Ferrero R, Labigne A. The role of the rdxA gene in the evolution of metronidazole resistance in Helicobacter pylori. J Antimicrob Chemother. 1999;43:753-8. http://dx.doi.org/10.1093/jac/43.6.753

Goodwin A, Kersulyte D, Sisson G, Veldhuyzen van Zanten SJ, Berg DE, Hoffman PS. Metronidazole resistance in Helicobacter pylori is due to null mutations in a gene (rdxA) that encodes an oxygen-insensitive NADPH nitroreductase. Mol Microbiol. 1998;28:383-93. http://dx.doi.org/10.1046/j.1365-2958.1998.00806.x

Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, et al. Management of Helicobacter pylori infection--the Maastricht IV/Florence consensus report. Gut. 2012;61:646-64. http://dx.doi.org/10.1136/gutjnl-2012-302084

Didelot X, Bowden R, Wilson DJ, Peto TE, Crook DW. Transforming clinical microbiology with bacterial genome sequencing. Nature Rev Genet. 2012;13:601-12. http://dx.doi.org/ 10.1038/nrg3226

Stolte M, Meining A. The updated Sydney system: Classification and grading of gastritis as the basis of diagnosis and treatment. Can J Gastroenterol. 2001;15:591-8. http://dx.doi.org/10.1155/2001/367832

Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis: The updated Sydney system. Am J Surg Pathol. 1996;20:1161-81. http://dx.doi.org/10.1097/00000478-199610000-00001

Acosta CP, Hurtado FA, Trespalacios AA. Determinación de mutaciones de un solo nucleótido en el gen 23S rRNA de Helicobacter pylori relacionadas con resistencia a claritromicina en una población del departamento del Cauca, Colombia. Biomédica. 2014;34:156-62. http://dx.doi.org/10.7705/biomedica.v34i0.1649

NCBI. Helicobacter pylori strain 26695-1MET, complete genome. Fecha de consulta: 26 de marzo de 2015. Disponible en: http://www.ncbi.nlm.nih.gov/nuccore/CP010436.1

Kwon D, Hulten K, Kato M, Kim J, Lee M, El-Zaatari F, et al. DNA sequence analysis of rdxA and frxA from 12 pairs of metronidazole-sensitive and-resistant clinical Helicobacter pylori isolates. Antimicrob Agents Chemother. 2001;45:2609-15. http://dx.doi.org/10.1128/AAC.45.9.2609-2615.2001

NCBI BLAST. NCBI BLAST: Basic Local Alignment Search Tool. Bethesda: National Library of Medicine. Fecha de consulta: 28 de junio de 2015. Disponible en: https://blast.ncbi.nlm.nih.gov/Blast.cgi

Bereswill S, Krainick C, Stähler F, Herrmann L, Kist M. Analysis of the rdxA gene in high-level metronidazoleresistant clinical isolates confirms a limited use of rdxA mutations as a marker for prediction of metronidazole resistance in Helicobacter pylori. FEMS Immunol Med Microbiol. 2003;36:193-8. http://dx.doi.org/10.1016/S0928-8244(03)00031-2

Tomb J-F, White O, Kerlavage AR, Clayton RA, Sutton GG, Fleischmann RD, et al. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997;388:539-47. http://dx.doi.org/10.1038/41483

EMBL-EBI. CLUSTALW2. Fecha de consulta: 3 de agosto de 2015. Disponible en: http://www.ebi.ac.uk/Tools/msa/clustalw2/

Kwon DH, Kato M, El-Zaatari FA, Osato MS, Graham DY. Frame-shift mutations in NAD (P) H flavin oxidoreductase encoding gene (frxA) from metronidazole resistant Helicobacter pylori ATCC43504 and its involvement in metronidazole resistance. FEMS Microbiol Lett. 2000;188:197-202. http://dx.doi.org/10.1111/j.1574-6968.2000.tb09193.x

Jeong J-Y, Mukhopadhyay AK, Dailidiene D, Wang Y, Velapatiño B, Gilman RH, et al. Sequential inactivation of rdxA (HP0954) and frxA (HP0642) nitroreductase genes causes moderate and high-level metronidazole resistance in Helicobacter pylori. J Bacteriol. 2000;182:5082-90. http://dx.doi.org/10.1128/JB.182.18.5082-5090.2000

Solcà NM, Bernasconi MV, Piffaretti J-C. Mechanism of metronidazole resistance in Helicobacter pylori: Comparison of the rdxA gene sequences in 30 strains. Antimicrob Agents Chemother. 2000;44:2207-10. http://dx.doi.org/10.1046/j.1469-0691.2000.00015.x

Teh X, Khosravi Y, Lee WC, Leow AH, Loke MF, Vadivelu J, et al. Functional and molecular surveillance of Helicobacter pylori antibiotic resistance in Kuala Lumpur. PLoS One. 2014;9:e101481. http://dx.doi.org/10.1371/journal.pone.0101481

Álvarez A, Moncayo JI, Santacruz JJ, Santacoloma M, Corredor LF, Reinosa E. Antimicrobial susceptibility and mutations involved in clarithromycin resistance in Helicobacter pylori isolates from patients in the western central region of Colombia. Antimicrob Agents Chemother. 2009;53:4022-4. http://dx.doi.org/10.1128/AAC.00145-09

Binh TT, Suzuki R, Trang TTH, Kwon DH, Yamaoka Y. Search for novel candidate mutations for metronidazole resistance in Helicobacter pylori using next-generation sequencing. Antimicrob Agents Chemother. 2015;59:2343-8. http://dx.doi.org/10.1128/AAC.04852-14

Wu W, Yang Y, Sun G. Recent insights into antibiotic resistance in Helicobacter pylori eradication. Gastroenterol Res Pract. 2012;2012:723183. http://dx.doi.org/10.1155/2012/723183

Rimbara E, Fischbach LA, Graham DY. Optimal therapy for Helicobacter pylori infections. Nat Rev Gastroenterol Hepatol. 2011;8:79-88. http://dx.doi.org/10.1038/nrgastro.2010.210

Heo J, Jeon SW. Optimal treatment strategy for Helicobacter pylori: Era of antibiotic resistance. World J Gastroenterol. 2014;20:5654-9. http://dx.doi.org/10.3748/wjg.v20.i19.5654

Greenberg ER, Anderson GL, Morgan DR, Torres J, Chey WD, Bravo LE, et al. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: A randomised trial. Lancet. 2011;378:507-14. http://dx.doi.org/10.1016/S0140-6736(11)60825-8

Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, et al. Current concepts in the management of Helicobacter pylori infection: The Maastricht III Consensus Report. Gut. 2007;56:772-81. http://dx.doi.org/10.1136/gut.2006.101634

Megraud F, Lamouliatte H. Review article: The treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther. 2003;17:1333-43. http://dx.doi.org/10.1046/j.1365-2036.2003.01592.x

Graham DY, Fischbach L. Helicobacter pylori treatment

in the era of increasing antibiotic resistance. Gut. 2010;59:1143-53. http://dx.doi.org/10.1136/gut.2009.192757

Trespalacios A, Otero W, Mercado M. Resistencia de Helicobacter pylori a metronidazol, claritromicina y amoxi-cilina en pacientes colombianos. Rev Colomb Gastroenterol. 2010;25:31-8.

Almeida N, Donato MM, Romãozinho JM, Luxo C, Cardoso O, Cipriano MA, et al. Beyond Maastricht IV: Are standard empiric triple therapies for Helicobacter pylori still useful in a South-European country? BMC Gastroenterol. 2015;15:23. http://dx.doi.org/10.1186/s12876-015-0245-y

Garza-González E, Pérez-Pérez G, Alanis-Aguilar O, Tijerina-Menchaca R, Maldonado-Garza H, Bosques-Padilla F. Antibiotic susceptibility patterns of Helicobacter pylori strains isolated from northeastern México. J Chemother. 2002;14:342-5. http://dx.doi.org/10.1179/joc.2002.14.4.342

Ogata SK, Gales AC, Kawakami E. Antimicrobial susceptibility testing for Helicobacter pylori isolates from Brazilian children and adolescents: Comparing agar dilution, E-test, and disk diffusion. Braz J Microbiol. 2014;45:1439-48. http://dx.doi.org/10.1590/S1517-83822014000400039

Gómez M, Otero W, Gutiérrez Ó. Tratamiento de la infec-ción por Helicobacter pylori. Encuesta en un grupo de médicos generales y especialistas en Colombia. Rev Colomb Gastroenterol. 2007;22:7-16.

How to Cite
1.
Acosta CP, Quiroga AJ, Sierra CH, Trespalacios AA. Frequency of Helicobacter pylori nitroreductase RdxA mutations for metronidazole activation in a population in the Cauca Department, Colombia. biomedica [Internet]. 2017 Jun. 1 [cited 2024 May 18];37(2):191-9. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/3007

Some similar items:

Published
2017-06-01
Section
Original articles

Altmetric

Article metrics
Abstract views
Galley vies
PDF Views
HTML views
Other views
QR Code