幽门螺杆菌克拉霉素耐药的基因诊断研究

张 焕乐, 程 毅东, 邓 敏, 林 秋满, 林 永恩
贺州市人民医院 广西贺州 542899

摘要

摘要：目的：本研究旨在评估探讨幽门螺杆菌耐药基因，寻找克拉霉素耐药的早期诊断基因，以期为临床诊治提供参考。方法：从胃炎患者体内分离到3株幽门螺杆菌耐药菌株。测定克拉霉素、甲硝唑和左氧氟沙星的最低抑菌浓度，并进行全基因组测序。用逆转录聚合酶链式反应检测到Hp1181和hp1184基因。用基因突变株和耐药株确定hp1181或hp1184与克拉霉素耐药的关系。通过全基因组检测和鉴定，鉴定菌株与hp26695的同源性。基因组序列、基因数量和对3株菌株进行了基因特征检测。耐药基因的预测和功能分析表明，hp1181和hp1184的RNA表达在三株菌中均升高，在人工诱导的克拉霉素耐药菌中也是如此。基因敲除后进行药敏试验。结果：在这些菌株中发现了与hp26695、hp1181和hp1184基因高度同源的菌株，hp1184和hp1181基因的表达与克拉霉素耐药有关。结论：Hp1181和hp1184突变可能是克拉霉素耐药最早和最持久的反应，它们可能是诊断、预防和治疗克拉霉素耐药的潜在靶基因。

关键词

关键词：幽门螺杆菌；克拉霉素耐药；基因诊断；幽门螺杆菌菌株

参考

[1]Bacic A, Milivojevic V, Petkovic I, et al. In Search for Reasons behindHelicobacter pylori Eradication Failure-Assessment of the AntibioticsResistance Rate and Co-Existence of Helicobacter pylori with CandidaSpecies[J]. J Fungi (Basel), 2023,9(3).[2]Gong Y, Zhai K, Sun L, et al. RdxA Diversity and MutationsAssociated with Metronidazole Resistance of Helicobacter pylori[J].Microbiol Spectr, 2023,11(2):e390322.[3]Adachi K, Kato S, Koshino A, et al. A Vonoprazan, Clarithromycin,and Metronidazole Regimen as Helicobacter pylori Eradication Therapy forPatients with Penicillin Allergy in Light of Clarithromycin Resistance[J]. Intern Med, 2023.[4]Lin Y, Shao Y, Yan J, et al. Antibiotic resistance in Helicobacterpylori: From potential biomolecular mechanisms to clinical practice[J]. JClin Lab Anal, 2023:e24885.[5]Lyu T, Cheung K S, Deng Z, et al. Whole genome sequencing revealsnovel genetic mutations of Helicobacter pylori associating with resistance toclarithromycin and levofloxacin[J]. Helicobacter, 2023:e12972.[6]Dascalu R I, Bolocan A, Paduaru D N, et al. Multidrug resistance inHelicobacter pylori infection[J]. Front Microbiol, 2023,14:1128497.[7]Zhang Y, Feng X, Bian L, et al. Antibiotic Resistance of Helicobacterpylori and Related Risk Factors in Yangzhou, China: A Cross-SectionalStudy[J]. J Clin Med, 2023,12(3).[8]Cho S H, Park M S, Park S Y, et al. Effectiveness of 7-day tripletherapy with half-dose clarithromycin for the eradication of Helicobacterpylori without the A2143G and A2142G point mutations of the 23S rRNAgene in a high clarithromycin resistance area[J]. Front Med (Lausanne),2023,10:1150396.[9]Feng S, Lin J, Zhang X, et al. Role of AlgC and GalU in the IntrinsicAntibiotic Resistance of Helicobacter pylori[J]. Infect Drug Resist,2023,16:1839-1847.[10]Orsten S, Yilmaz E, Akyon Y. Molecular Characterization ofClarithromycin Resistance in Helicobacter pylori Strains[J]. Turk JGastroenterol, 2023.[11]Mormeneo B S, Belles B A, Vazquez G D, et al. AntibioticSusceptibility and Clarithromycin Resistance Determinants in Helicobacterpylori in the Northeast of Spain: A One-Year Prospective Study[J]. Antibiotics(Basel), 2023,12(2).[12]Fauzia K A, Aftab H, Tshibangu-Kabamba E, et al. MutationsRelated to Antibiotics Resistance in Helicobacter pylori Clinical Isolatesfrom Bangladesh[J]. Antibiotics (Basel), 2023,12(2).[13]Galos F, Boboc C, Iesanu M I, et al. Antibiotic Resistance andTherapeutic Efficacy of Helicobacter pylori Infection in Pediatric Patients-ATertiary Center Experience[J]. Antibiotics (Basel), 2023,12(1).[14]Boyanova L, Gergova G, Kandilarov N, et al. Geographic distributionof antibiotic resistance of Helicobacter pylori: A study in Bulgaria[J]. ActaMicrobiol Immunol Hung, 2023,70(1):79-83.[15]Megraud F, Graham D Y, Howden C W, et al. Rates of AntimicrobialResistance in Helicobacter pylori Isolates From Clinical Trial PatientsAcross the US and Europe[J]. Am J Gastroenterol, 2023,118(2):269-275.[16]Bailey K S, Brown H E, Lekic V, et al. Helicobacter pylori treatmentknowledge, access and barriers: A cross-sectional study[J]. Helicobacter,2023,28(2):e12954.[17]Borka B R, Melit L E, Marginean C O. Current Worldwide Trends inPediatric Helicobacter pylori Antimicrobial Resistance[J]. Children (Basel),2023,10(2).[18]Shrestha A B, Pokharel P, Sapkota U H, et al. Drug ResistancePatterns of Commonly Used Antibiotics for the Treatment of Helicobacterpylori Infection among South Asian Countries: A Systematic Review andMeta-Analysis[J]. Trop Med Infect Dis, 2023,8(3).[19]Sholeh M, Khoshnood S, Azimi T, et al. The prevalence ofclarithromycin-resistant Helicobacter pylori isolates: a systematic reviewand meta-analysis[J]. PeerJ, 2023,11:e15121.[20]Wang Y Z, Chen J, Pei S Q, et al. Treatment strategies andpharmacist-led medication management for Helicobacter pylori infection[J].Drug Dev Res, 2023,84(2):326-336.