Cirz Ryan T, O'Neill Bryan M, Hammond Jennifer A, Head Steven R, Romesberg Floyd E
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
J Bacteriol. 2006 Oct;188(20):7101-10. doi: 10.1128/JB.00807-06.
Pseudomonas aeruginosa infections can be virtually impossible to eradicate, and the evolution of resistance during antibiotic therapy is a significant concern. In this study, we use DNA microarrays to characterize the global transcriptional response of P. aeruginosa to clinical-like doses of the antibiotic ciprofloxacin and also to determine the component that is regulated by LexA cleavage and the SOS response. We find that genes involved in virtually every facet of metabolism are down-regulated in response to ciprofloxacin. The LexA-controlled SOS regulon identified by microarray analysis includes only 15 genes but does include several genes that encode proteins involved in recombination and replication, including two inducible polymerases known to play a role in mutation and the evolution of antibiotic resistance in other organisms. The data suggest that the inhibition of LexA cleavage during therapy might help combat this pathogen by decreasing its ability to adapt and evolve resistance.
铜绿假单胞菌感染实际上可能无法根除，抗生素治疗期间耐药性的演变是一个重大问题。在本研究中，我们使用DNA微阵列来表征铜绿假单胞菌对临床剂量抗生素环丙沙星的全局转录反应，并确定受LexA切割和SOS反应调控的成分。我们发现，几乎参与新陈代谢各个方面的基因在对环丙沙星的反应中均被下调。通过微阵列分析鉴定出的LexA控制的SOS调节子仅包含15个基因，但确实包括几个编码参与重组和复制的蛋白质的基因，其中包括两种已知在其他生物体的突变和抗生素耐药性演变中起作用的诱导型聚合酶。数据表明，治疗期间抑制LexA切割可能有助于对抗这种病原体，通过降低其适应和产生耐药性的能力。
