Abstract
In order for a drug to inhibit microbial growth it must reach an inhibitory concentration at its target site. The drug has therefore to penetrate the various permeability barriers that separate its target site from the external environment. Differences in the properties of these permeability barriers among the various species of micro-organisms are important in determining the antimicrobial spectrum of a drug. For example, a specific isolated target site prepared from different bacteria may be inhibited to a similar extent by an antibacterial agent in vitro, whereas the intact organisms may exhibit a range of sensitivities to the same drug. This can often be explained by species differences in the structure and composition of the cell envelopes that influence the access of drugs to the target sites. As we shall see, the intracellular concentrations of antimicrobial drugs can also be profoundly affected by the activities of drug efflux systems.
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Further reading
Hancock, R. E. W. (1997). The bacterial outer membrane as a drug barrier.Trends Microbiol. 5, 37.
Nikaido, H. (1994). Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264, 382.
Nikaido, H. (1996). Multidrug efflux pumps of Gram- negative bacteria. J. Bact. 178, 5853.
Nikaido, H. and Thanassi, D. G. (1993). Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples. Antimicrob. Agents Chemother. 37, 1393.
Paulsen, I. T., Brown, M. H. and Skurray, R. A. (1996). Proton-dependent multidrug efflux systems. Microbiol. Rev. 60, 575.
Tute, M. S. (1972). Principles and practice of Hansch analysis: a guide to the structure-activity relationships for the medicinal chemist. Adv. Drug. Res. 6, 1.
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© 1998 The Kluwer Academic Publishers
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Franklin, T.J., Snow, G.A. (1998). Penetrating the defences: how antimicrobial drugs reach their targets. In: Biochemistry and Molecular Biology of Antimicrobial Drug Action. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-9127-5_7
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DOI: https://doi.org/10.1007/978-94-010-9127-5_7
Publisher Name: Springer, Dordrecht
Print ISBN: 978-0-412-82190-5
Online ISBN: 978-94-010-9127-5
eBook Packages: Springer Book Archive