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Antimicrobial Agents and Chemotherapy, February 2000, p. 311-315, Vol. 44, No. 2
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Substitutions in the Eyelet Region Disrupt Cefepime Diffusion through the Escherichia coli OmpF Channel

Valérie Simonet, Monique Malléa, and Jean-Marie Pagès*

CJF 9606, Faculté de Médecine, 13385 Marseille Cedex 05, France

Received 19 March 1999/Returned for modification 14 September 1999/Accepted 1 November 1999

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.

* Corresponding author. Mailing address: CJF 9606 INSERM, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France. Phone: 33 4 91 32 45 87. Fax: 33 4 91 32 46 06. E-mail: Jean-Marie.Pages{at}medecine.univ-mrs.fr.

Antimicrobial Agents and Chemotherapy, February 2000, p. 311-315, Vol. 44, No. 2
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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