Exploring Non-QRDR Mutations in gyrA and gyrB and Their Impact on Quinolone Resistance in Helicobacter pylori
7
Issued Date
2025-03-01
Resource Type
ISSN
15982467
Scopus ID
2-s2.0-105004988003
Journal Title
Journal of Bacteriology and Virology
Volume
55
Issue
1
Start Page
54
End Page
68
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Bacteriology and Virology Vol.55 No.1 (2025) , 54-68
Suggested Citation
Lee D.H., Thi O.D., Ha J.H., Choi J.G., Kim K.M., Trinh M.P., Anh W.J., Kang K.M., Park J.S., Byun J.H., Lee W.K., Jung M.H., Boonyanugomol W., Baik S.C., Kang H.L., Shin M.K. Exploring Non-QRDR Mutations in gyrA and gyrB and Their Impact on Quinolone Resistance in Helicobacter pylori. Journal of Bacteriology and Virology Vol.55 No.1 (2025) , 54-68. 68. doi:10.4167/jbv.2025.55.1.054 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110269
Title
Exploring Non-QRDR Mutations in gyrA and gyrB and Their Impact on Quinolone Resistance in Helicobacter pylori
Corresponding Author(s)
Other Contributor(s)
Abstract
This study investigates the role of mutations in the quinolone resistance-determining regions (QRDR) and beyond in the gyrA and gyrB genes of Helicobacter pylori, specifically their contributions to quinolone resistance. While QRDR mutations are well-established as key contributors to resistance, the impact mutations outside the QRDR remains less understood. Using clinical isolates from Korean pediatric patients, the study analyzed both QRDR and non-QRDR mutations through natural transformation and molecular docking to assess their effects on resistance and the ciprofloxacin (CIP) binding structure. Mutations were identified in both gyrA and gyrB, with non-QRDR mutations at positions 134, 190, 705, and 709 in gyrA, and 249 and 624 in gyrB. These non-QRDR mutations were not directly linked to quinolone resistance. However, molecular docking analysis of the 91st position in gyrA revealed significant alterations in the CIP binding structure, which were strongly associated with increased resistance. Moreover, the A134V mutation, although outside the QRDR, was found to accelerate the emergence of spontaneous QRDR mutations, suggesting an indirect role in resistance development. These findings underscore the critical importance of QRDR mutations in H. pylori quinolone resistance, with particular emphasis on the mutation at position 91 of gyrA, which significantly alters the CIP binding structure and correlates with increased resistance. The study provides valuable insights into the mechanisms of antibiotic resistance, enhancing the understanding of H. pylori resistance pathways and informing future research toward developing more effective treatment strategies.