Kayama Shizuo, Murakami Keiji, Ono Tsuneko, Ushimaru Makiko, Yamamoto Akitake, Hirota Katsuhiko, Miyake Yoichiro
Department of Oral Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
FEMS Microbiol Lett. 2009 Sep;298(2):184-92. doi: 10.1111/j.1574-6968.2009.01717.x. Epub 2009 Jul 7.
The basis of the bactericidal action of antibiotics and the mechanisms of antibiotic tolerance are largely unknown. To elucidate one of the mechanisms of antibiotic tolerance, the present study investigated the role of Pseudomonas aeruginosa quorum sensing (QS) and the rpoS gene in antibiotic tolerance. The survival rates of the lasR and lasI mutants were observed to be lower than that of the parental strain in time-dependent killing studies with 8 microg mL(-1) ofloxacin, but the survival rates of the rhlR and rhlI mutants were not different from that of the parental strain. Moreover, a lasR-overexpressing strain was more tolerant to ofloxacin than the parental strain, but this was not the case for an rhlR-overexpressing strain. The mRNA expression levels of lasR, lasI, and rpoS in the wild-type strain in the presence of bactericidal concentration of ofloxacin were lower than that in the absence of ofloxacin. In addition, the significant loss of antibiotic tolerance in the lasR mutant was recovered by the overexpression of rpoS. These results suggest that the Las QS system in P. aeruginosa is involved in the development of ofloxacin tolerance, and the tolerance induced by the Las-system is regulated by rpoS gene.
抗生素杀菌作用的基础以及抗生素耐受性的机制在很大程度上尚不清楚。为了阐明抗生素耐受性的机制之一,本研究调查了铜绿假单胞菌群体感应(QS)和rpoS基因在抗生素耐受性中的作用。在使用8μg/mL左氧氟沙星的时间依赖性杀伤研究中,观察到lasR和lasI突变体的存活率低于亲本菌株,但rhlR和rhlI突变体的存活率与亲本菌株没有差异。此外,lasR过表达菌株比亲本菌株对左氧氟沙星更具耐受性,但rhlR过表达菌株并非如此。在存在杀菌浓度左氧氟沙星的情况下,野生型菌株中lasR、lasI和rpoS的mRNA表达水平低于不存在左氧氟沙星时的表达水平。此外,rpoS的过表达恢复了lasR突变体中显著丧失的抗生素耐受性。这些结果表明,铜绿假单胞菌中的Las QS系统参与了左氧氟沙星耐受性的形成,并且Las系统诱导的耐受性受rpoS基因调控。