THIOLACTOMYCIN RESISTANCE IN ESCHERICHIA-COLI IS ASSOCIATED WITH THE MULTIDRUG-RESISTANCE EFFLUX PUMP ENCODED BY EMRAB
THIOLACTOMYCIN RESISTANCE IN ESCHERICHIA-COLI IS ASSOCIATED WITH THE MULTIDRUG-RESISTANCE EFFLUX PUMP ENCODED BY EMRAB
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DOI：
10.1128/jb.175.12.3723-3729.1993
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发表时间：
1993-06-01
影响因子：
3.2
通讯作者：
ROCK, CO
中科院分区：
文献类型：
--
作者：
FURUKAWA, H;TSAY, JT;ROCK, CO
硫代actomycin （TLM）和cerulenin是通过抑制β -酮酰基-酰基载体蛋白合成酶I步骤的脂肪酸生物合成来阻断大肠杆菌生长的抗生素。TLM和蓝蓝蛋白都能触发细胞内丙二酰辅酶A的积累，同时抑制生长，并且合酶I蛋白的过度表达赋予了对这两种抗生素的抗性。菌株CDM5是一种tlm抗性突变体，但对蓝紫蛋白敏感。TLM既没有诱导丙二酰辅酶A的积累，也没有阻断脂肪酸的产生；而菌株CDM5提取物的脂肪酸合成酶活性对TLM的抑制较为敏感。菌株CDM5的TLM抗性基因定位在染色体57.5 min，是emrB基因的一个等位基因。emrB基因的破坏将菌株CDM5转化为TLM敏感菌株，并且emrAB操纵子的过表达赋予TLM对敏感菌株的抗性。因此，emr外排泵的激活是菌株CDM5对TLM耐药的机制。
Thiolactomycin (TLM) and cerulenin are antibiotics that block Escherichia coli growth by inhibiting fatty acid biosynthesis at the beta-ketoacyl-acyl carrier protein synthase I step. Both TLM and cerulenin trigger the accumulation of intracellular malonyl-coenzyme A coincident with growth inhibition, and the overexpression of synthase I protein confers resistance to both antibiotics. Strain CDM5 was derived as a TLM-resistant mutant but remained sensitive to cerulenin. TLM neither induced malonyl-coenzyme A accumulation nor blocked fatty acid production in vivo; however, the fatty acid synthase activity in extracts from strain CDM5 was sensitive to TLM inhibition. The TLM resistance gene in strain CDM5 was mapped to 57.5 min of the chromosome and was an allele of the emrB gene. Disruption of the emrB gene converted strain CDM5 to a TLM-sensitive strain, and the overexpression of the emrAB operon conferred TLM resistance to sensitive strains. Thus, activation of the emr efflux pump is the mechanism for TLM resistance in strain CDM5.