The role of rpoS gene and quorum-sensing systemin ofloxacin tolerance in Pseudomonas aeruginosa

The role of rpoS gene and quorum-sensing systemin ofloxacin tolerance in Pseudomonas aeruginosa
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DOI:
10.1111/j.1574-6968.2009.01717.x
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发表时间:
2009-09-01
影响因子:
2.1
通讯作者:
Miyake, Yoichiro
Miyake, Yoichiro
中科院分区:
生物学4区
文献类型:
--
作者:
Kayama, Shizuo;Murakami, Keiji;Miyake, Yoichiro

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抗生素杀菌作用的基础和抗生素耐药的机制在很大程度上还不清楚。为了阐明铜绿假单胞菌耐药的机制之一,本研究探讨了铜绿假单胞菌群体感应(QS)和rpoS基因在抗生素耐药中的作用。在8mU·g·L~(-1)氧氟沙星的时间依赖杀伤实验中,LasR和LASI突变体的存活率低于亲本菌株,而rh lR和rh lI突变体的存活率与亲本菌株无差异。此外,LasR高表达菌株对氧氟沙星的耐受性高于亲本菌株,但rHLR高表达菌株的情况并非如此。野生型菌株在有杀菌浓度氧氟沙星时,LasR、LASI和rpos的mRNA表达水平低于无杀菌浓度的野生型菌株。此外,rpos的过表达还恢复了LasR突变体对抗生素耐受性的显著丧失。这些结果表明,铜绿假单胞菌中的LAS-QS系统参与了氧氟沙星耐受性的形成,由LAS-系统诱导的耐受性受rpos基因的调控。
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 mu g 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.