Bacterial energetics and antimicrobial resistance.

Defining resistance to antimicrobics with specific terms is very useful as the precise mechanisms often lead to better susceptibility testing and improved treatment of bacterial infections. When one can characterize a class of phenotypic resistant organisms as electron transport variants, this has value in that it provides information about the basis for resistance and removes them from the non-specific categorization as phenotypically resistant. Studies of bacterial small colony variants (SCVs) has provided new insights into antimicrobial resistance as well as the connection between expression of virulence factors and energy metabolism. It also provides a framework for further studies which link antibiotic resistance to phase of growth, availability of nutrients, other environmental conditions, and adaptations to stress into a single model wherein the bacterial cell uses the products of energy metabolism to detect its sense of well being and to alter its response to antibiotics (Fig. I). Levels of NADH and ATP are able to act as signaling molecules in both gram positive an gram negative bacteria to activate stress sigma factors and two component systems. In the future, a full understanding of the signaling pathways in bacterial pathogens may provide new targets for the development of drugs to reduce bacterial virulence and to enhance the activity of existing antibiotics.