Marrer Estelle, Satoh A Tatsuo, Johnson Margaret M, Piddock Laura J V, Page Malcolm G P
The University of Texas Health Science Center at San Antonio, Texas 78229-3900, USA.
Antimicrob Agents Chemother. 2006 Jan;50(1):269-78. doi: 10.1128/AAC.50.1.269-278.2006.
Streptococcus pneumoniae M22 is a multidrug-resistant mutant selected after exposure of capsulated wild-type S. pneumoniae NCTC 7465 (strain M4) to ciprofloxacin. DNA microarray analysis comparing the gene expression profiles of strain M22 with those of strain M4 showed that strain M22 constitutively expressed 22 genes at levels higher than those observed in strain M4 under all conditions studied. These included the genes encoding the enzymes involved in branched-chain amino acid biosynthesis and two genes (patA and patB) with sequences suggestive of ABC transporter proteins. Expression of the patA and patB genes was induced by ciprofloxacin in both strains, but in strain M4 it only reached the levels observed in strain M22 after long incubation with high concentrations of ciprofloxacin. The altered expression profile observed with strain M22 suggested that the mutation or mutations acquired during resistance selection bring the cell into a state in which the expression of critical genes is preemptively altered to correct for the potential effects of ciprofloxacin on gene expression in the parent strain.
肺炎链球菌M22是一种多重耐药突变体，它是在将有荚膜的野生型肺炎链球菌NCTC 7465（菌株M4）暴露于环丙沙星后筛选得到的。通过DNA微阵列分析比较菌株M22和菌株M4的基因表达谱，结果显示在所有研究条件下，菌株M22组成性表达22个基因，其表达水平高于菌株M4中观察到的水平。这些基因包括编码参与支链氨基酸生物合成的酶的基因，以及两个序列提示为ABC转运蛋白的基因（patA和patB）。在两种菌株中，环丙沙星均可诱导patA和patB基因的表达，但在菌株M4中，只有在与高浓度环丙沙星长时间孵育后，其表达水平才达到菌株M22中观察到的水平。在菌株M22中观察到的表达谱改变表明，在耐药性选择过程中获得的一个或多个突变使细胞进入一种状态，在这种状态下，关键基因的表达被预先改变，以纠正环丙沙星对亲本菌株基因表达的潜在影响。
