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2025 Vol.55, Issue 1 Preview Page

Original Article

Exploring Non-QRDR Mutations in gyrA and gyrB and Their Impact on Quinolone Resistance in Helicobacter pylori
Dong-Hae Lee12†
,
Oanh Dao Thi12†
,
Jong-Hun Ha12
,
Jeong-Gyu Choi123
,
Kyu-Min Kim12
,
Minh Phuong Trinh12
,
Won Jun Anh12
,
Kyung-Min Kang123
,
Jin-Sik Park1
,
Jung-Hyun Byun34
,
Woo-Kon Lee123
,
Myung Hwan Jung123
,
Wongwarut Boonyanugomol5
,
Seung-Chul Baik12
,
Hyung-Lyun Kang12*
,
Min-Kyoung Shin123*
1Department of Microbiology, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
2Department of Convergence Medical Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea
3Fastidious Specialized Pathogen Resources Bank, a member of the National Culture Collection for Pathogens, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea
4Department of Laboratory Medicine, College of Medicine, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea
5Department of Sciences and Liberal Arts, Mahidol University, Amnatcharoen Campus, Amnatcharoen, Thailand
*kangssi@gnu.ac.kr
*mkshin@gnu.ac.kr
†These authors equally contributed to this work.
31 March 2025. pp. 54-68
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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.

Keywords
Helicobacter pylori
Quinolone resistance
DNA gyrase
Quinolone resistance determining region (QRDR)
Spontaneous mutations
Molecular docking
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Information
  • Publisher :The Korean Society for Microbiology and The Korean Society of Virology
  • Publisher(Ko) :대한미생물학회‧대한바이러스학회
  • Journal Title :JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • Volume : 55
  • No :1
  • Pages :54-68
  • Received Date : 2025-02-13
  • Revised Date : 2025-03-10
  • Accepted Date : 2025-03-11
  • DOI :https://doi.org/10.4167/jbv.2025.55.1.054
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