Identify the non-synonymous mutations bearing on gyrA and gyrB genes of Helicobacter pylori strains among patient with peptic ulcer disease

Tran Thi Nhu Le, Nguyen Vu Trung, Tran Ngoc Anh

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Abstract

Peptic ulcer disease is one of five leading causes of hospitalization. The most common cause of peptic ulcer disease is H. pylori infection which represented from 50% to 70.3%. In term of H. pylori treatment, the antibiotic resistant of H. pylori is the most concerning issue which woud determined a successful therapy. Consequently, it is important to evaluate the antibiotic resistant among antibiotics that are presently prescribed in H. pylori eradication regimens and to update the clinical guideline on the treatment and management of H. pylori infection. The E-test method is performed to evaluate the minimum inhibitory concentration (MIC) of levofloxacin and identify the point mutation on gyrA and gyrB gene to explore the molecular genetic resistant mechanism. The results showed that among samples, the levofloxacin resistant strains occupied 56.9%. There are 4 important mutations among gyrA gene found including N87K(12.3%), N87Y(1.5%), D91N(1.5%), D91G(3.1%). Besides, we found one novel mutation S457A in gyrB. Notably, the bearing point mutation strains had significant higher MIC level when compared with those with no mutation (p < 0.05). In conclusion, we suggest to study the point mutation of gyrA and gyrB to regulate the antibiotic resistant of H. pylori as well as to determine the therapeutic dosage of levofloxacin.

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References

1. Tonolini M, Ierardi AM, Bracchi E, Magistrelli P, Vella A, Carrafiello G. Non-perforated peptic ulcer disease: multidetector CT findings, complications, and differential diagnosis. Insights into imaging. Oct 2017;8(5):455-469. doi:10.1007/s13244-017-0562-5.
2. Vương Tuyết Mai, Nguyễn Khánh Trạch và Phùng Đắc Cam (2001). Kết quả nghiên cứu tỉ lệ nhiễm Helicobacter pylori ở 528 người khỏe mạnh. Tạp chí nội khoa, 4, 22-26.
3.Kavitt RT, Lipowska AM, Anyane-Yeboa A, Gralnek IM. Diagnosis and Treatment of Peptic Ulcer Disease. The American journal of medicine. Apr 2019;132(4):447-456. doi:10.1016/j.amjmed.2018.12.009.
4.Alarcon T, Urruzuno P, Martinez MJ, et al. Antimicrobial susceptibility of 6 antimicrobial agents in Helicobacter pylori clinical isolates by using EUCAST breakpoints compared with previously used breakpoints. Enfermedades infecciosas y microbiologia clinica. May 2017;35(5):278-282. doi:10.1016/j.eimc.2016.02.010.
5.Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Alimentary pharmacology & therapeutics. Jan 1 2006;23(1):35-44. doi:10.1111/j.1365-2036.2006.02737.
6. Hanafi A, Lee WC, Loke MF, et al. Molecular and Proteomic Analysis of Levofloxacin and Metronidazole Resistant Helicobacter pylori. Frontiers in microbiology. 2016;7:2015. doi:10.3389/fmicb.2016.02015
7. Hofreuter D, Behrendt J, Franz A, et al. Antimicrobial resistance of Helicobacter pylori in an eastern German region. Helicobacter. Feb 2021;26(1):e12765. doi:10.1111/hel.12765.
8. Losurdo G, Giorgio F, Pricci M, et al. Helicobacter pylori Primary and Secondary Genotypic Resistance to Clarithromycin and Levofloxacin Detection in Stools: A 4-Year Scenario in Southern Italy. Antibiotics. Oct 21 2020;9(10)doi:10.3390/antibiotics9100723.
9. Rhie SY, Park JY, Shin TS, Kim JW, Kim BJ, Kim JG. Discovery of a Novel Mutation in DNA Gyrase and Changes in the Fluoroquinolone Resistance of Helicobacter pylori over a 14-Year Period: A Single Center Study in Korea. Antibiotics. May 27 2020;9(6)doi:10.3390/antibiotics9060287.
10. Trần Thiện Trung, Nguyễn Tuấn Anh, Trần Thiện Khiêm. Nghiên cứu đột biến kháng Clarithromycin và Levofloxacin của vi khuẩn H.pylori bằng giải trình tự gen. Tạp chí khoa học tiêu hóa việt nam. 2014;9(37):2367-2375.
11. Muhammad Miftahussurur&Yoshio Yamaoka (2015), Appropriate firstline regimens to combat Helicobacter pylori antibiotic resistance: an Asian perspective, Molecules (Basel, Switzerland). 20 (4): 6068-6092.
12. Binkowska A, Biernat MM, Laczmanski L, Gosciniak G. Molecular Patterns of Resistance Among Helicobacter pylori Strains in South-Western Poland. Frontiers in microbiology. 2018;9:3154. doi:10.3389/fmicb.2018.03154.
13. Đặng Ngọc Quý Huệ. Nghiên cứu tỉ lệ kháng Clarithromycin, Levofloxacin của Helicobacter pylori bằng Epsilometer và hiệu quả của phác đồ EBMT ở bệnh nhân viêm dạ dày mạn. Trường Đại học Y Dược Huế. 2018.
14. Wang D, Guo Q, Yuan Y, Gong Y. The antibiotic resistance of Helicobacter pylori to five antibiotics and influencing factors in an area of China with a high risk of gastric cancer. BMC microbiology. Jul 4 2019;19(1):152. doi:10.1186/s12866-019-1517-4
15. Nguyễn Thị Chi, Trần Duy Hưng, Trần Ngọc Ánh. Tình hình kháng kháng sinh của Helicobacter pylori tại Bệnh viện Đại học Y Hà Nội từ 2017-2019. Tạp chí Y học thực hành. 5/2020: 1133, 92-96