Guzman Kevin, Montenegro Lidia, Pazos Alvaro
Grupo Salud Pública, Centro de Estudios en Salud Universidad de Nariño (CESUN), Universidad de Nariño, Pasto, Colombia.
Departamento de Biología, Universidad de Nariño, Pasto, Colombia.
Front Microbiol. 2023 Jul 7;14:1198325. doi: 10.3389/fmicb.2023.1198325. eCollection 2023.
The eradication of () using multiple therapies is used as a prevention strategy. However, its efficacy has been compromised by the emergence of single nucleotide polymorphisms in genes associated with resistance to multiple antibiotics. To estimate antibiotic resistance rates associated with mutations in genes in the high-cancer-risk population in Colombia, we included 166 whole genome sequences from a cohort of individuals with a high risk of gastric cancer. By using the reference strain ATCC 26695, we identified mutations in specific genes to evaluate resistance rates for different antibiotics: rRNA for clarithromycin, rRNA for tetracycline, for amoxicillin, for levofloxacin, and for metronidazole. The phylogenomic analysis was conducted using the core genome consisting of 1,594 genes of -ATCC 26695. Our findings revealed that the resistance rate of to clarithromycin was 3.62%, primarily associated with mutations A2143G and A2142G in the rRNA gene. For tetracycline, the resistance rate was 7.23%, with mutations A926G, A926T, and A928C observed in the rRNA gene. Amoxicillin resistance was found in 25.9% of cases, with observed mutations in the gene, including T556S, T593, R649K, R656P, and R656H. In the gene, mutations N87K, N87I, D91G, D91N, and D91Y were identified, resulting in a resistance rate of 12.04% to levofloxacin. The most common mutations in the gene associated with metronidazole resistance were a stop codon, and mutations at D59N and D59S, resulting in a resistance rate of 99.3%. The high resistance rate of to metronidazole indicated that this drug should be excluded from the eradication therapy. However, the resistance rates for tetracycline and clarithromycin did not exceed the established resistance threshold in Colombia. The increased resistance rate of to levofloxacin and amoxicillin may partially explain the observed therapeutic failures in Colombia. The phylogenomic tree showed that the isolate belongs to its own lineage (hspColombia). These findings offer valuable insights to enhance the characterization of treatment protocols for the specific lineage (hspColombia) at the local level.
采用多种疗法根除()作为一种预防策略。然而,与多种抗生素耐药相关基因中出现的单核苷酸多态性削弱了其疗效。为了估计哥伦比亚高癌症风险人群中与()基因中的突变相关的抗生素耐药率,我们纳入了来自胃癌高风险人群队列的166个全基因组序列。通过使用参考菌株ATCC 26695,我们鉴定了特定基因中的突变,以评估不同抗生素的耐药率:克拉霉素的rRNA、四环素的rRNA、阿莫西林的()、左氧氟沙星的()以及甲硝唑的()。使用由-ATCC 26695的1594个基因组成的核心基因组进行系统基因组分析。我们的研究结果显示,()对克拉霉素的耐药率为3.62%,主要与rRNA基因中的A2143G和A2142G突变相关。对于四环素,耐药率为7.23%,在rRNA基因中观察到A926G、A926T和A928C突变。25.9%的病例中发现阿莫西林耐药,在()基因中观察到突变,包括T556S、T593、R649K、R656P和R656H。在()基因中,鉴定出N87K、N87I、D91G、D91N和D91Y突变,导致对左氧氟沙星的耐药率为12.04%。与甲硝唑耐药相关基因中最常见的突变是一个终止密码子,以及D59N和D59S处的突变,导致耐药率为99.3%。()对甲硝唑的高耐药率表明该药物应被排除在根除治疗之外。然而,四环素和克拉霉素的耐药率未超过哥伦比亚既定的耐药阈值。()对左氧氟沙星和阿莫西林耐药率的增加可能部分解释了在哥伦比亚观察到的治疗失败情况。系统基因组树显示()分离株属于其自己的谱系(hsp哥伦比亚)。这些发现为在地方层面加强针对特定()谱系(hsp哥伦比亚)的治疗方案的特征描述提供了有价值的见解。