Two different types of fosfomycin resistance in clinical isolates of Klebsiella pneumoniae.
Two different types of fosfomycin resistance in clinical isolates of Klebsiella pneumoniae.
复制标题
肺炎克雷伯菌临床分离株中两种不同类型的磷霉素耐药性。
DOI：
10.1111/j.1574-6968.1993.tb06543.x
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发表时间：
1993
影响因子：
2.1
通讯作者：
Koji O'hara
中科院分区：
文献类型：
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作者：
Koji O'hara
对100株肺炎克雷伯菌临床分离株进行磷霉素敏感性测定，并分析耐药株的耐药机制。从菌株中制备的洗涤细胞显示磷霉素的MIC大于8微克ml-1使药物失活。对磷霉素高度耐药的Tf 129 B菌株的粗提物用于研究药物失活酶的酶性质。灭活的最适pH为7.8，反应的最适温度为37 ℃。已证明谷氨酰胺在失活中作为辅因子是有效的。提示肺炎克雷伯菌的灭活酶为磷霉素：谷胱甘肽-S-转移酶，是一种位于周质间隙的组成性酶。发现该酶的比活性与MIC水平之间存在良好的相关性;然而，某些菌株显示出低水平的磷霉素：谷胱甘肽-S-转移酶活性，这不能解释MIC的增加。菌株Tf 129 B和Tf 408 E均显示磷霉素的MIC大于1024 μ g ml-1，携带可转移的耐药质粒。在菌株Tf 129 B中，磷霉素抗性的机制是由于高水平的酶活性。在菌株Tf 408 E中，确定主要是由于细胞膜的渗透性降低。
The fosfomycin susceptibility of 100 clinical isolates of Klebsiella pneumoniae and the resistance mechanisms utilized by resistant strains were examined. Washed cells prepared from the strains demonstrating MICs of more than 8 micrograms ml-1 of fosfomycin inactivated the drug. A crude extract from strain Tf129B, highly resistant to fosfomycin, was used to study the enzymatic properties of the drug-inactivating enzyme. The optimum pH for inactivation was 7.8 and the optimum temperature of the reaction was 37 degrees C. Glutathione was shown to be effective as a cofactor in the inactivation. It was suggested that the inactivating enzyme of Klebsiella pneumoniae was fosfomycin: glutathione-S-transferase, a constitutive enzyme located in the periplasmic space. A good correlation was found between the specific activities of this enzyme and the MIC levels; however, certain strains showed a low level of fosfomycin:glutathione-S-transferase activity which could not account for the increased MIC. Strains Tf129B and Tf408E, both demonstrating MICs of more than 1024 micrograms ml-1 of fosfomycin carried a transferable resistance plasmid. In strain Tf129B, the mechanism of fosfomycin resistance was due to a high level of enzymic activity. In strain Tf408E, it was determined to be mainly due to the reduced permeability of the cell membrane.