Morrow T O, Harmon S A
J Bacteriol. 1979 Jan;137(1):374-83. doi: 10.1128/jb.137.1.374-383.1979.
Spontaneous mutants of Staphylococcus aureus resistant to rifampin, rifamycin SV, streptovaricin, or streptolydigin were isolated and shown to be resistant due to chromosomal rather than plasmid mutations. Based on data concerning spontaneous mutation rates, genetic cotransduction rates, and in vitro sensitivity studies, four major antibiotic cross-resistance patterns were found. The genetic markers responsible for these cross-resistance patterns were shown to be separable by transduction. Nonpurified RNA polymerase activity in lysates of mutants showed the same sensitivity to these antibiotics as shown by the mutants on solid media. A model is proposed explaining possible structure-function relationships involved in the binding of these antibiotics to the RNA polymerase molecule and the mutations resulting in resistance to these antibiotics. This model includes generally overlapping but different-sized binding sites on the RNA polymerase protein coded for by similarly arranged mutable sites on the DNA.
分离出了对利福平、利福霉素SV、链霉素或链溶菌素具有抗性的金黄色葡萄球菌自发突变体，并证明其抗性是由染色体突变而非质粒突变引起的。基于有关自发突变率、基因共转导率和体外敏感性研究的数据，发现了四种主要的抗生素交叉抗性模式。这些交叉抗性模式所涉及的遗传标记可通过转导分离。突变体裂解物中的未纯化RNA聚合酶活性对这些抗生素的敏感性与突变体在固体培养基上所显示的相同。提出了一个模型，解释了这些抗生素与RNA聚合酶分子结合以及导致对这些抗生素产生抗性的突变中可能涉及的结构-功能关系。该模型包括RNA聚合酶蛋白上通常重叠但大小不同的结合位点，这些位点由DNA上类似排列的可变位点编码。
