UNDERSTANDING CELLULAR-RESPONSES TO TOXIC AGENTS - A MODEL FOR MECHANISM-CHOICE IN BACTERIAL METAL RESISTANCE

Bacterial resistances to metals are heterogeneous in both their geneti c and biochemical bases. Metal resistance may be chromosomally-, plasm id- or transposon-encoded, and one or more genes may be involved; at t he biochemical level at least six different mechanisms are responsible for resistance. Various types of resistance mechanisms can occur sing ly or in combination and for a particular metal different mechanisms o f resistance can occur in the same species. To understand better the d iverse responses of bacteria to metal ion challenge we have constructe d a qualitative model for the selection of metal resistance in bacteri a. How a bacterium becomes resistant to a particular metal depends on the number and location of cellular components sensitive to the specif ic metal ion. Other important selective factors include the nature of the uptake systems for the metal, the role and interactions of the met al in the normal metabolism of the cell and the availability of plasmi d (or transposon) encoded resistance mechanisms. The selection model p resented is based on the interaction of these factors and allows predi ctions to be made about the evolution of metal resistance in bacterial populations. It also allows prediction of the genetic basis and of me chanisms of resistance which are in substantial agreement with those i n well-documented populations. The interaction of, and selection for r esistance to, toxic substances in addition to metals, such as antibiot ics and toxic analogues, involve similar principles to those concernin g metals. Potentially, models for selection of resistance to any subst ance can be derived using this approach.