Department of Medical Microbiology and Molecular Epidemiology, Pediatric Research and Clinical Center for Infectious Diseases, Saint Petersburg, Russia.
Department of Medical Microbiology, North-Western State Medical University named after I.I. Mechnikov, Saint Petersburg, Russia.
Microb Drug Resist. 2019 Dec;25(10):1401-1409. doi: 10.1089/mdr.2019.0130. Epub 2019 Jul 19.
The pathways in the development of ceftaroline resistance of methicillin-resistant (MRSA) isolates belonging to the ST8, ST239, and ST228 were evaluated. Ceftaroline-resistant derivatives were isolated through selection during 40 passages. Ceftaroline MIC measurements and whole-genome sequencing were performed after 5, 20, and 40 passages. In two ST8 derivative isolates, ceftaroline MIC increased up to 128 mg/L. Mutations were acquired in and in one isolate after 20 passages and in in another after 40 passages. MIC for two ST239 derivatives increased to 128 mg/L. Substitutions in Pbp4 and polymorphisms in the upstream region of were identified in both derivatives after 40 passages. In one isolate, additional mutation in and deletion in were detected. In an ST228 derivative, MIC increased to 32 mg/L with one mutation in penicillin-binding protein 2a (Y446N) detected after five passages and a second (E447K) after 20 passages. Three pathways in the development of ceftaroline resistance were identified. For ST8 and ST239 derivatives mutations were detected in and , respectively, whereas in ST228 - in . Most derivatives harbored additional mutations whose potential role in the development of resistance has not been determined.
评估了耐甲氧西林金黄色葡萄球菌（MRSA）ST8、ST239 和 ST228 株中头孢洛林耐药的发展途径。通过 40 次传代选择分离出头孢洛林耐药衍生物。在 5、20 和 40 次传代后进行头孢洛林 MIC 测量和全基因组测序。在两个 ST8 衍生株中，头孢洛林 MIC 增加到 128 mg/L。在一个 20 次传代后和另一个 40 次传代后，在 和 中获得了突变。两个 ST239 衍生物的 MIC 增加到 128 mg/L。在两个衍生物中，在 40 次传代后鉴定出 Pbp4 中的取代和 的上游区域的多态性。在一个分离株中，还检测到 在 和 中的缺失。在 ST228 衍生株中，MIC 增加到 32 mg/L，在 5 次传代后检测到青霉素结合蛋白 2a（Y446N）中的一个突变，在 20 次传代后检测到第二个突变（E447K）。确定了头孢洛林耐药发展的三种途径。在 ST8 和 ST239 衍生物中分别检测到 和 中的突变，而在 ST228 中 - 在 中。大多数衍生物还携带额外的突变，其在耐药发展中的潜在作用尚未确定。
