PMID:10639355
| Citation |
Simonet, V, Malléa, M and Pagès, JM (2000) Substitutions in the eyelet region disrupt cefepime diffusion through the Escherichia coli OmpF channel. Antimicrob. Agents Chemother. 44:311-5 |
|---|---|
| Abstract |
The Escherichia coli OmpF porin is a nonspecific channel involved in the membrane translocation of small hydrophilic molecules and especially in the passage of beta-lactam antibiotics. In order to understand the dynamic of charged-compound uptake through bacterial porins, specific charges located in the E. coli OmpF channel were mutated. Substitutions G119D and G119E, inserting a protruding acidic side chain into the pore, decreased cephalosporin and colicin susceptibilities. Cefepime diffusion was drastically altered by these mutations. Conversely, substitutions R132A and R132D, changing a residue located in the positively charged cluster, increased the rate of cephalosporin uptake without modifying colicin sensitivity. Modelling approaches suggest that G119E generates a transverse hydrogen bond dividing the pore, while the two R132 substitutions stretch the channel size. These charge alterations located in the constriction area have differential effects on cephalosporin diffusion and substantially modify the profile of antibiotic susceptibility. |
| Links | |
| Keywords |
Anti-Bacterial Agents/pharmacology; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Cephalosporins/metabolism; Colicins/pharmacology; Escherichia coli/drug effects; Escherichia coli/metabolism; Microbial Sensitivity Tests; Models, Molecular; Mutagenesis; Porins/genetics; Porins/metabolism; Protein Folding |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.