??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????
?????????????????????????????????????OmpA?OmpF?OmpC,??????????????????????????????????????????1??
??OmpF?????????????????????OmpF??????????????????????????????????????OmpC??????????????????????????????????????????????????2??
??????????Red??????OmpF????F-M-2/OmpFΔ?????????????β-????????????????????????????????????
??1?????
??1.1??
????????????????????????F-M-2??????????OmpF????F-M-2/OmpFΔ????????
??1.2????
?????????????Oxoid???????????????????????????????????????
??1.3????
?????????????F-M-2??????F-M-2/OmpFΔ????????5mL LB???????37??220r/min???????????? ? ? ? ? ? ?1?100? ? ? ? ? ? ? ?100mL?LB????????????OD600??0.6????25?25mL???????6mLLB??????????F-M-2??????F-M-2/OmpFΔ?????12?????1?????????????25????37??200r/min?????????
??1.4??OD600????
??????0?1.5?3?4?6?8?10?12?14?16?18?20h,????F-M-2????F-M-2/OmpFΔ???1?????OD600???????????????????????????
??1.5????
??????????????????CLSI??????????K-B????????F-M-2????F-M-2/OmpFΔ?β-?????8??????????????????MH???????WHO?????????????????????LB???????????5mL?????????37???4~8h,??????????0.5????????????????????MH?????????????10min????????????????????37 ???15min,?????16~18h??????
??1.6???????β-???????MIC????
??MIC????CLSI??????????????????????????????????????????????????0.5???????50!L??????????????????????????13????????1???1.6mL????????????1mL,??1?????????????1 280μg/mL?0.4mL???????1mL??2????????1mL??3????????????11?????11????1mL????12?????????????13????????????
?????????????256?128?64?32?16?8?4?2?1?0.5?0.25μg/mL.?????????????????1mL,???????????5×105CFU/mL.????1???11??????? ?128?64?32?16?8?4?2?1?0.5?0.25?0.125μg/mL.????????????????????????75%??????37 ????18h???????????????????????????????????????????????????????MIC.
??2?????
??2.1????????????????
??????????F-M-2?F-M-2/OmpFΔ?????????????????????????OD600????????????????F-M-2??????F-M-2/OmpFΔ????????1???
F-M-2?F-M-2/OmpFΔ?LB? ? ? ??OmpF???????????????????????OD600?????????
??2.2?????????????
??????????β-?????8?????????????1.
???β-??????????8??????????????F-M-2/OmpFΔ????F-M-2?????????????????CZ?CFP?CAZ????????????? ?CRO?AMP?VI?MPN?????????????????????IPM???????????????
??2.3???????MIC????
??????CLSI???MIC????????????????MIC????CLSI????????????????MIC????????MIC??????????3??????????????????MIC??????????2.
??MIC???????????β-????????
??CZ?CFP?AMP?CRO?CAZ?CTX?????????CZ?CAZ?????CFP?AM?CRO????????CRO?????????64??
??3??
????1929?????Penicillin???????β-????????????????????????????β-????????????????????????????????β-???????????????β-?????????????????????????????????????????????OmpF?OmpC,???OmpF???????????????????????????????????????????????
??OmpF???????????????????????????????????????????????????????????????????3????????????F-M-2????F-M-2/OmpFΔ???LB???????37???????????????????????????4???????????????????????????4????14h???F-M-2/OmpFΔ?OD600??????????F-M-2/OmpFΔ?????????????17h??????????????????OmpF???F-M-2/OmpFΔ???????????????????????????????????????????????????????????????????????????
???????F-M-2/OmpFΔ?IPM????????????????????OmpF????????????????????????????MIC?????????????OmpF????????????????OmpF??????β-???????????????????????????????OmpF??????????OmpF???????????????????????????????????????????????????5???????????????????????????????????????????????????????????????????So Youn??6???????????35KDa?36KDa??????OMPs?????????????????????????????????OmpF??β-?????????????
??Brigitte??7????????????????OmpF????????????β-???????????????????????????????????????????PBPs????????????????7?PBPs,PBP1A?PBP1B???????????????β-???????????????????PBP1A?PBP1B??????????????8?????OmpF??????????????????????β-????????????????????β-??????????????
??????
???1?Kumar A,Schweizer H P.Bacterial resistance to antibiot-ics:active efflux and reduced uptake?J??Adv Drug DelivRev,2005,57?10??1486~1513.
???2?Andersen C,Hughes C,Koronakis V.Protein export anddrug efflux through bacterial channel-tunnels?J??CurrOpin Cell Biol,2001,13?4??412~416.
???3????????????????????????????D??????????2006:44.
???4?????????????????M?????????????2010:27~28.
???5????????????????????????β-?????????????????????J????????????2010,10?6??472~476.