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| Content Provider | PubMed Central |
|---|---|
| Author | Spratt, Brian G. |
| Abstract | The 6-β-amidinopenicillanic acid derivative, mecillinam, was highly specific in its action on the growth of Escherichia coli. Concentrations from the minimal inhibitory concentration (0.05 μg/ml) up to at least 200 μg/ml resulted in the conversion of E. coli rods into osmotically stable spherical cells without significantly inhibiting cell growth or causing cell lysis. A second amidinopenicillanic acid derivative [6-([4-morpholinylmethylene] amino) penicillanic acid] showed identical effects on cell growth at concentrations from its minimal inhibitory concentration (0.2 μg/ml) up to at least 5 μg/ml but, at higher concentrations, increasing amounts of lysis occurred. Neither of these compounds showed the immediate inhibition of cell division that is observed with typical β-lactam antibiotics. We have compared the binding of these two amidinopenicillanic acids to the individual penicillin-binding proteins of E. coli. Both compounds showed a high specificity of binding to penicillin-binding protein 2 at low concentrations. At higher concentrations mecillinam still maintained its high specificity for protein 2 and very little binding of mecillinam to any of the other binding proteins was detected with concentrations up to 1 mg/ml. The morpholino compound, however, showed extensive binding to proteins 1 and 4, and slight binding to proteins 5 and 6 at high concentrations. The morpholino compound therefore combined both the physiological properties and the binding properties of mecillinam with some of those of typical penicillins and cephalosporins. Lysis probably occurs at high concentrations of morpholino compound because it binds to penicillin-binding protein 1, since this is believed to be the target with which β-lactams interact to inhibit cell elongation. |
| Starting Page | 161 |
| File Format | |
| ISSN | 10986596 |
| e-ISSN | 10986596 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Issue Number | 1 |
| Volume Number | 11 |
| Language | English |
| Publisher Date | 1977-01-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Pharmacology Pharmacology (medical) |
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