Cell wall thickening is associated with adaptive resistance to amikacin in methicillin-resistant Staphylococcus aureus clinical isolates.
Cell wall thickening is associated with adaptive resistance to amikacin in methicillin-resistant Staphylococcus aureus clinical isolates.
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DOI：
10.1093/jac/dks522
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发表时间：
2013-05
期刊：
影响因子：
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通讯作者：
Wenchang Yuan;Qiwen Hu;Hang Cheng;Weilong Shang;Nan Liu;Ziyu Hua;Junmin Zhu;Zhen Hu;Jizhen Yuan-Jiz
中科院分区：
文献类型：
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作者：
Wenchang Yuan;Qiwen Hu;Hang Cheng;Weilong Shang;Nan Liu;Ziyu Hua;Junmin Zhu;Zhen Hu;Jizhen Yuan-Jiz
耐甲氧西林金黄色葡萄球菌（MRSA）感染正在增加，引起全球关注。MRSA对阿米卡星耐药的机制知之甚少。我们报告的第一个配对研究，揭示了MRSA的表型细胞壁增厚与适应性耐药性阿米卡星。方法从1例12岁男性骨髓炎患者的血液和关节液中分离出2株MRSA（CY 001和CY 002）。对分离菌株进行药敏试验、分子分型、形态学观察和体外诱导耐药试验。结果两株MRSA均为Panton-Valentine杀白细胞素阳性、多位点序列型59、葡萄球菌盒式染色体mec IV型和spa型437，PFGE图谱完全一致。两株菌的药敏谱相似。然而，CY 001对阿米卡星耐药（CY 001-AMI（R）; MIC = 64 mg/L），与敏感CY 002（CY 002-AMI（S）; MIC = 8 mg/L）相反。CY 001-AMI（R）可能已经产生了适应性耐药性，因为它缺乏氨基糖苷类修饰酶，并且生长曲线改变。有趣的是，在阿米卡星存在下，CY 001-AMI（R）在其MIC下具有比CY 002-AMI（S）（18.15 ± 3.74 nm）更厚的细胞壁（36.43 ± 4.25 nm）。在阿米卡星的MIC（36.78 ± 3.41 nm）存在下，在体外诱导的菌株（CY 002-AMI（R））中也可以观察到增厚的细胞壁;该菌株是通过逐渐增加阿米卡星的量获得的。然而，在阿米卡星存在下培养的细胞壁增厚的菌株仍然对万古霉素敏感。结论：细胞壁增厚与耐甲氧西林金黄色葡萄球菌的适应性耐药有关，当对阿米卡星产生适应性耐药时，可使用替代抗生素治疗患者。
OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) infection is increasing and causing global concern. The mechanism of MRSA resistance to amikacin is poorly understood. We report on the first matched-pair study to reveal that the phenotypic cell wall thickening of MRSA is associated with adaptive resistance to amikacin. METHODS Two MRSA strains (CY001 and CY002) were isolated from blood and synovial fluid samples, respectively, from a 12-year-old male patient with osteomyelitis. The strains were subjected to a matched-pair study, including antimicrobial agent susceptibility determination, molecular typing, morphological observation and in vitro resistance induction. RESULTS Both strains are Panton-Valentine leucocidin-positive, multilocus sequence type 59, staphylococcal cassette chromosome mec type IV and spa type 437 MRSA with identical PFGE profiles. The drug susceptibility spectra of the two isolates are similar. However, CY001 is resistant to amikacin (CY001-AMI(R); MIC = 64 mg/L), contrary to the susceptible CY002 (CY002-AMI(S); MIC = 8 mg/L). CY001-AMI(R) may have developed adaptive resistance, because it lacks aminoglycoside-modifying enzymes and has an altered growth curve. Interestingly, CY001-AMI(R) has a thicker cell wall (36.43 ± 4.25 nm) than CY002-AMI(S) (18.15 ± 3.74 nm) in the presence of amikacin at its MIC. The thickened cell wall can also be observed in an in vitro-induced strain (CY002-AMI(R)) in the presence of amikacin at its MIC (36.78 ± 3.41 nm); this strain was obtained by gradually increasing the amount of amikacin. However, the cell wall-thickened strains cultured in the presence of amikacin are still susceptible to vancomycin. CONCLUSIONS Cell wall thickening is associated with adaptive resistance in MRSA and alternative antibiotics can be used to treat patients when adaptive resistance to amikacin has developed.