Tsuruoka T, Miyata A, Inouye S
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Jpn J Antibiot. 1996 Sep;49(9):892-8.
The mutation sites in FR182 and FR190, which were selected as fosfomycin (FOM) resistant mutants in vitro from an Escherichia coli (E. coli) K-12 derivative, were found to be close to the 52 min. and the 85 min., respectively, on linkage map of E. coli K-12. Therefore, the site of mutation in FR182 appears to be ptsI and that in FR190 to be cyaA based on the physiological and biochemical characteristics. We isolated isogenic transductants from the FOM resistant strains (from FR182, resistant strain AMG3 and sensitive strain AMG4, and from FR190, resistant strain AMI5 and sensitive strain AMI6) by transducing the genes of the resistant strains into recipients that were deficient in alkaline phosphatase. Under anaerobic conditions, MICs in the isogenic transductants were all decreased and the resistant transductants showed similar FOM sensitivities to the respective sensitive transductants. The FOM resistant strains were clearly lysed by much lower concentrations of FOM in the presence of cyclic adenosine-3',5'-monophosphate (cAMP) or glucose 6-phosphate (G6P) than in their absence, but the extent of lysis was more pronounced when both cAMP and G6P were present together, resembling the lysis of sensitive strains in same condition.
FR182和FR190中的突变位点，是从大肠杆菌（E. coli）K-12衍生物中体外筛选出的磷霉素（FOM）抗性突变体，发现它们分别靠近大肠杆菌K-12连锁图谱上的52分钟和85分钟处。因此，基于生理生化特性，FR182中的突变位点似乎是ptsI，FR190中的突变位点似乎是cyaA。我们通过将抗性菌株的基因导入碱性磷酸酶缺陷的受体中，从FOM抗性菌株（来自FR182的抗性菌株AMG3和敏感菌株AMG4，以及来自FR190的抗性菌株AMI5和敏感菌株AMI6）中分离出同基因转导子。在厌氧条件下，同基因转导子中的最低抑菌浓度（MIC）均降低，抗性转导子对相应敏感转导子表现出相似的FOM敏感性。与不存在环磷酸腺苷（cAMP）或6-磷酸葡萄糖（G6P）时相比，在存在cAMP或G6P的情况下，FOM抗性菌株明显被低得多浓度的FOM裂解，但当cAMP和G6P同时存在时，裂解程度更明显，类似于在相同条件下敏感菌株的裂解。
