Volff J N, Vandewiele D, Decaris B
Laboratoire de Génétique et Microbiologie, Unité associée INRA, Faculté des Sciences, Université de Nancy I, Vandoeuvre-lès-Nancy, France.
Antimicrob Agents Chemother. 1994 Sep;38(9):1984-90. doi: 10.1128/AAC.38.9.1984.
In Streptomyces ambofaciens NSA2002, pigmented wild-type colonies spontaneously give rise to pigment-negative (Pig-) mutants at a frequency of about 0.5%. This genetic instability is related to large deletions which can be associated with amplifications of DNA sequences. The influence of three fluoroquinolones (ciprofloxacin, enoxacin, and norfloxacin) on this property was investigated. At a survival rate higher than 60%, most colonies showed a patchwork phenotype consisting of phenotypically heterogeneous colonies harboring numerous mutant sectors. Moreover, the frequency of Pig- mutants rose to more than 90% at survival rates equal to or higher than 10%. Induced Pig- mutants showed the same phenotypical features as did spontaneous mutants. Most of them also harbored deletions, associated in some cases with DNA amplifications, in two loci of the large unstable region, AUD6 and AUD90 (derived from amplifiable unit of DNA). The size of deletions in induced mutants could rise to 1.5 Mb. These results show that ciprofloxacin, enoxacin, and norfloxacin greatly stimulate genetic instability and the occurrence of DNA rearrangements in S. ambofaciens. Moreover, these three fluoroquinolones had the same rank order for both toxic (i.e., antibacterial) and genotoxic activities. If the antibacterial effect of fluoroquinolones in S. ambofaciens is due to their interference with DNA gyrase, as shown for some other organisms, the genotoxic effect observed could be due to their interaction with this type II topoisomerase. This suggests that DNA gyrase is involved in the process of genetic instability in S. ambofaciens.
在产二素链霉菌NSA2002中，色素野生型菌落会以约0.5%的频率自发产生色素阴性（Pig-）突变体。这种遗传不稳定性与大片段缺失有关，这些缺失可能与DNA序列的扩增相关。研究了三种氟喹诺酮类药物（环丙沙星、依诺沙星和诺氟沙星）对该特性的影响。在存活率高于60%时，大多数菌落呈现出由含有众多突变区域的表型异质菌落组成的拼接表型。此外，在存活率等于或高于10%时，Pig-突变体的频率上升至90%以上。诱导产生的Pig-突变体表现出与自发突变体相同的表型特征。它们中的大多数在大的不稳定区域的两个位点AUD6和AUD90（源自可扩增DNA单元）也存在缺失，在某些情况下与DNA扩增相关。诱导突变体中的缺失大小可能增至1.5 Mb。这些结果表明，环丙沙星、依诺沙星和诺氟沙星极大地刺激了产二素链霉菌的遗传不稳定性和DNA重排的发生。此外，这三种氟喹诺酮类药物在毒性（即抗菌）和基因毒性活性方面具有相同的排序。如果氟喹诺酮类药物在产二素链霉菌中的抗菌作用如在其他一些生物体中所示是由于它们对DNA回旋酶的干扰，那么观察到的基因毒性作用可能是由于它们与这种II型拓扑异构酶的相互作用。这表明DNA回旋酶参与了产二素链霉菌的遗传不稳定过程。
