Host-Pathogen Interactions Unit, Research Institute for Medicines (iMed-ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal.
Department of Biochemistry and Human Biology, Faculty of Pharmacy, Universidade de Lisboa, 1649 003 Lisbon, Portugal.
Microb Genom. 2020 Mar;6(3). doi: 10.1099/mgen.0.000344.
For a long time infections have been treated using the macrolide antibiotic, clarithromycin. Clarithromycin resistance is increasing worldwide and is the most common cause of treatment failure. Here we review the mechanisms of antibiotic resistance to clarithromycin, detailing the individual and combinations of point mutations found in the 23S rRNA gene associated with resistance. Additionally, we consider the methods used to detect clarithromycin resistance, emphasizing the use of high-throughput next-generation sequencing methods, which were applied to 17 newly sequenced pairs of strains isolated from the antrum and corpus of a recent colonized paediatric population. This set of isolates was composed of six pairs of resistant strains whose phenotype was associated with two point mutations found in the 23S rRNA gene: A2142C and A2143G. Other point mutations were found simultaneously in the same gene, but, according to our results, it is unlikely that they contribute to resistance. Further, among susceptible isolates, genomic variations compatible with mutations previously associated with clarithromycin resistance were detected. Exposure to clarithromycin may select low-frequency variants, resulting in a progressive increase in the resistance rate due to selection pressure.
长期以来，感染一直使用大环内酯类抗生素克拉霉素进行治疗。克拉霉素耐药性在全球范围内不断增加，是治疗失败的最常见原因。在这里，我们回顾了克拉霉素耐药的机制，详细说明了与耐药性相关的 23S rRNA 基因中发现的单个和组合点突变。此外，我们还考虑了检测克拉霉素耐药性的方法，强调了使用高通量下一代测序方法的应用，该方法应用于最近定植的儿科人群的胃窦和胃体中分离的 17 对新测序的菌株。这组分离物由六对耐药菌株组成，其表型与 23S rRNA 基因中的两个点突变相关：A2142C 和 A2143G。在同一基因中还发现了其他点突变，但根据我们的结果，它们不太可能导致耐药性。此外，在敏感分离物中，检测到与克拉霉素耐药相关的先前突变相容的基因组变异。克拉霉素的暴露可能选择低频变异体，由于选择压力导致耐药率逐渐增加。
