Various membrane active antibiotics, including polymyxin and octapeptin, have served as useful tools for studying the structure and function ofbiolog ical membranes (1-9). In addition, a number of the peptide antibiotics have strong affinities for membrane lipids, and therefore can be used as well defined model systems for studying the chemistry of lipid-peptide interac tions (3, 10, 1 1). A prerequisite for the application of these antibiotics as probes of membrane structure and function is a detailed description of the mechanism for their antimicrobial activities. The objective of this chapter is to review the research concerning the mechanism of action of the poly myxins and several related peptides. The peptides under consideration in clude the polymyxins, octapeptins, brevistin, stendomycin, polypeptin, and cerexin, all of which have been isolated from various Bacillus strains. These antibiotics are grouped together because they are all cyclic polycationic peptides, containing a high percentage of diaminobutyric acid with a fatty acid attached through an amide linkage. In addition, there is some evidence that the polymyxins and octapeptins affect bacterial membrane structure and function in a similar manner (9). The first of these peptides to be isolated were the polymyxins, which were obtained from a strain of Bacillus polymyxa in 1947 (12-14). The circulins and colistins were originally thought to be quite distinct from the polymyx ins but were later correctly classified as polymyxins (15, 16). Octapeptin, also referred to as EM 49 (17), brevistin (18-21), stendomycin (22), poly peptin (23), and cerexin (20) have all been isolated andlor characterized within the last seven years. The polymyxins and octapeptins have been studied most extensively; however, the other members of this family of peptides may ultimately expand the range of compounds available for struc ture-function correlations. One of the objectives of this review is to compare and contrast the effects of the polymyxins and octapeptins on bacterial membranes.

It is well-established that the polymyxins and octapeptins alter bacterial membrane structure (9, 24), although the detailed mechanisms for their antimicrobial activities are still undefined. The amphipathic character of these peptides might suggest that their disruptive influence on membrane structure is completely analogous to simple cationic detergents. However, these antibiotics exhibit biostatic or biocidal activities at concentrations much lower than the common cationic detergents (9). Furthermore, rela tively minor structural modifications of these peptides can result in signifi cant changes in their biological activities. These general observations suggest that interactions between these antibiotics and bacterial membranes involve some degree of specificity beyond that expected for simple deter-