MACROLIDE TRANSPORT IN ESCHERICHIA-COLI STRAINS HAVING NORMAL AND ALTERED OMPC AND OR OMPF PORINS

被引:10
作者
CAPOBIANCO, JO
GOLDMAN, RC
机构
[1] Anti-infective Research Division, Department 47 M, Abbott Laboratories, Abbott Park, IL 60064-3500, Building AP9A, One Abbott Park Road
关键词
PORIN MUTANTS; ESCHERICHIA-COLI; ERYTHROMYCIN; AZITHROMYCIN; TRANSPORT;
D O I
10.1016/0924-8579(94)90007-8
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
[C-14]Erythromycin and [C-14]azithromycin uptake rates were studied in Escherichia coli strains containing normal OmpC and OmpF porins (strain MCR106) and altered OmpC porins due to small insertions (strains RAM121 and OC1555) or deletions (strain RAM122) in the ompC alleles and altered OmpF porins due to small ompF deletions (strains OC1555 and PLB3255). Strains RAM121 and RAM122 also lacked OmpF porins in their outer membrane. The porin mutants demonstrated a 2- to 1224-fold increase in macrolide transport and a concurrent 3- to 530-fold decrease in MIC when compared to the parent strain, MCR1O6. Both strains OC1555 and PLB3255 had enhanced permeability to 1-N-phenylnaphthylamine indicating increased permeability of the outer membrane to hydrophobic molecules. The macrolides, at 2 to 1000 times MIC, failed to displace the cationic probe polymyxin; therefore, drug entry by a self-promoted mechanism was not indicated. Since >95% of macrolide is protonated and thus hydrophilic (logP(i) = -0.89) at neutral pH, the bulk of drug entry may be via the porin channels.
引用
收藏
页码:183 / 189
页数:7
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