Penetrating the defences: how antimicrobial drugs reach their targets

  • T. J. Franklin
  • G. A. Snow


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.


Outer Membrane Cytoplasmic Membrane Passive Diffusion Periplasmic Space Proton Motive Force 
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Further reading

  1. Hancock, R. E. W. (1997). The bacterial outer mem- brane as a drug barrier. Trends Microbiol. 5, 37.PubMedCrossRefGoogle Scholar
  2. Nikaido, H. (1994). Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264, 382.PubMedCrossRefGoogle Scholar
  3. Nikaido, H. (1996). Multidrug efflux pumps of Gram-negative bacteria. J. Bact. 178, 5853.PubMedGoogle Scholar
  4. Nikaido, H. and Thanassi, D. G. (1993). Penetration of lipophilic agents with multiple protonation sites intoGoogle Scholar
  5. bacterial cells: tetracyclines and fluoroquinolones as examples. Antimicrob. Agents Chemother. 37, 1393.Google Scholar
  6. Paulsen, I. T., Brown, M. H. and Skurray, R. A. (1996). Proton-dependent multidrug efflux systems. Microbiol. Rev. 60, 575.PubMedGoogle Scholar
  7. 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.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • T. J. Franklin
    • 1
  • G. A. Snow
    • 1
  1. 1.Zeneca PharmaceuticalsMacclesfield, CheshireUK

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