The effect of small interfering RNA against Pseudomonas aeruginosa expressing MexA-MexB-OprM efflux pumps in vivo
10.3760/cma.j.issn.0254-5101.2012.11.006
- VernacularTitle:siRNA干扰铜绿假单胞菌MexAB-OprM外排泵MexB基因表达的体内效应研究
- Author:
Fengyun GONG
;
Dingyu ZHANG
;
Jiangguo ZHANG
;
Weili ZHAN
;
Ying SONG
;
Jueping FENG
;
Jianxin SONG
- Publication Type:Journal Article
- Keywords:
siRNA;
Pseudomonas aeruginosa;
MexB gene;
MexAB-OprM efflux pump
- From:
Chinese Journal of Microbiology and Immunology
2012;(11):944-948
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the efficacy of small interfering RNA against Pseudomonos aeruginosa expressing MexA-MexB-OprM multidrug efflux pump in vivo.Methods Two short hairpin (sh)RNA expression vectors targeting the MexB gene,and negative controls,were designed,synthesized,and electrotransformed into the P.aeruginosa strain PAO1.The in vivo therapeutic efficacy of the MexB small interfering (si)RNAs was determined by infecting a murine model of chronic P.aeruginosa lung infection (1 × 107 CFU/ml).The mice were killed on day 3,5 and 7 after infection with the Pseudomonas aeruginosa strains.Results In the murine infection model,treatment with MexB-siRNAs led to significantly reduced bacteria burden of the bellows by day 5 and 7 post-infection,and reduced the P.aeruginosa-induced pathological changes.In addition,MexB-siRNA2 treatment enhanced neutrophil recruitment and production of inflammatory cytokines (IL-1β,IL-12) in the early infection stage (day 3) (P＜0.05),both of which decreased by day 7.Conclusion MexB-siRNA could inhibit both mRNA expression and the activity of P.aeruginosa in vitro.siRNA was effective in reducing the bacterial load in a murine model of chronic lung infection.Targeting of MexB with siRNA appears to be a novel strategy for treating P.aeruginosa infections.
