Fauzia Kartika Afrida, Aftab Hafeza, Tshibangu-Kabamba Evariste, Alfaray Ricky Indra, Saruuljavkhlan Batsaikhan, Cimuanga-Mukanya Alain, Matsumoto Takashi, Subsomwong Phawinee, Akada Junko, Miftahussurur Muhammad, Yamaoka Yoshio
Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Japan.
Department of Public Health and Preventive Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60115, Indonesia.
Antibiotics (Basel). 2023 Jan 31;12(2):279. doi: 10.3390/antibiotics12020279.
Current management of gastric inflammation involves the eradication of . However, the effectiveness of commonly used antibiotics against infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as , , , , , , and ) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher's exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance ( = 0.000018) but not in locus A2146G ( = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) ( = 0.002) and N87K ( = 0.002) of was associated with levofloxacin resistance. Mutations in locus A343V ( = 0.041) of also showed a significant association. Meanwhile, in the gene, several mutations might explain the resistance; they were G594fs ( = 0.036), K306R ( = 0.036), N562Y ( = 0.0006), and V45I ( = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in .
目前胃炎的治疗包括根除幽门螺杆菌。然而，由于抗生素耐药性，常用抗生素对抗幽门螺杆菌感染的有效性已有所下降。基于表型的诊断方法费力，且难以找出耐药原因。因此，有必要尽早检测并了解这种耐药性的潜在机制。本研究评估了来自孟加拉国受试者临床分离株中与抗菌药物耐药性（AMR）相关基因的突变情况。对56株分离株进行了全基因组测序，并提取了相关基因（如幽门螺杆菌的23S rRNA、16S rRNA、gyrA、gyrB、rpoB、rpsL、pbp1A和pbp2B）。对读取序列进行组装，并通过用于抗生素突变分析的最新流程ARIBA提取单核苷酸多态性（SNP）。使用Fisher精确检验评估突变及其与抗生素表型的关联。在本研究中，克拉霉素耐药率很高，为39.3%（22/56），MIC中位数为24 mg/L，范围在2至128 mg/L之间。A2147G突变与耐药性显著相关（P = 0.000018），但A2146G位点则不然（P = 0.056）。左氧氟沙星也表现出较高的耐药性。我们观察到gyrA基因的D91N（而非D91Y）（P = 0.002）和N87K（P = 0.002）突变与左氧氟沙星耐药性相关。rpoB基因A343V位点的突变（P = 0.041）也显示出显著关联。同时，在pbp1A基因中，有几个突变可能解释其耐药性；它们分别是G594fs（P = 0.036）、K306R（P = 0.036）、N562Y（P = 0.0006）和V45I（P = 0.018）。甲硝唑的耐药率异常高（96.4%），且在相关基因中发生了大量突变,包括基因截断。这些结果表明，抗生素靶蛋白编码基因的突变仍是幽门螺杆菌耐药的关键机制。
