This chapter discusses the types of transport systems that confer resistance to antibiotics, antimicrobial drugs, and toxic metals. A number of these are discussed in detail in other chapters, so here we focus on the ways in which microorganisms have evolved to use transporters to evade the toxic effects of drugs and metals.
Resistance to therapeutic drugs and toxic metals encompasses a diverse range of biological systems, all of which have an impact on humans. From the relative simplicity of bacterial cells, fungi, and protozoa to the complexity of human cancer cells, resistance has become problematic. One of the most frequently employed strategies for resistance to cytotoxic compounds and elements in both prokaryotes and eukaryotes is extrusion from the cell catalyzed by membrane transporters. These effl ux proteins reduce their intracellular concentration to subtoxic levels (1). Although some of these transporters extrude specifi c drugs and metals, others can extrude a wide range of structurally dissimilar drugs. Currently, much research is directed toward understanding the molecular mechanisms of these transport proteins. Potential clinical applications include the design of inhibitors that block these effl ux systems. Clinically useful inhibitors could allow a renaissance for drugs rendered obsolete by the development of effl ux systems in both prokaryotes and eukaryotes.