Vuorio R, Vaara M
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Antimicrob Agents Chemother. 1992 Apr;36(4):826-9. doi: 10.1128/AAC.36.4.826.
The conditionally lethal lpxA2 mutant of Escherichia coli, which lacks detectable UDP-N-acetylglucosamine acyltransferase activity and which produces greatly reduced amounts of lipid A after a shift to 42 degrees C (S. Galloway and C. R. H. Raetz, J. Biol. Chem. 265:6394-6402, 1990), was found to be, at conditions which promote normal growth, remarkably susceptible to a number of antibiotics. The MICs of hydrophobic antibiotics, such as rifampin, erythromycin, clindamycin, and fusidic acid, were 32- to greater than 128-fold lower for the lpxA2 strain than for the parent type strain, and those of the peptide antibiotics vancomycin and bacitracin were 32- and 256-fold lower, respectively. Futhermore, the lpxA2 strain was found to be sensitive to hypoosmotic conditions. Comparisons with the other characterized outer membrane permeability mutants, such as the heptose-deficient strains of E. coli and Salmonella typhimurium, the acrA and abs mutants of E. coli, and the ssc-1 and class SS-B mutants of S. typhimurium, indicated that the lpxA2 mutant had characteristically the most antibiotic-supersusceptible phenotype. These findings advocate the possible use of the lpxA2 strain as a tool in various fields of basic and applied bacterial research in which the impermeability of the outer membrane currently poses problems.
大肠杆菌的条件致死性lpxA2突变体缺乏可检测到的UDP-N-乙酰葡糖胺酰基转移酶活性，在转移至42℃后产生的脂多糖A量大幅减少（S. 加洛韦和C. R. H. 雷茨，《生物化学杂志》265:6394 - 6402，1990），发现在促进正常生长的条件下，该突变体对多种抗生素异常敏感。对于lpxA2菌株，疏水性抗生素如利福平、红霉素、克林霉素和夫西地酸的最低抑菌浓度（MIC）比亲本型菌株低32至大于128倍，肽类抗生素万古霉素和杆菌肽的MIC分别低32倍和256倍。此外，发现lpxA2菌株对低渗条件敏感。与其他已鉴定的外膜通透性突变体进行比较，如大肠杆菌和鼠伤寒沙门氏菌的庚糖缺陷菌株、大肠杆菌的acrA和abs突变体以及鼠伤寒沙门氏菌的ssc - 1和SS - B类突变体，表明lpxA2突变体具有典型的最易被抗生素超敏的表型。这些发现表明lpxA2菌株有可能作为一种工具应用于基础和应用细菌研究的各个领域，在外膜通透性目前造成问题的情况下。
