Biophysical analysis of membrane-targeting antimicrobial peptides: membrane properties and the design of peptides specifically targeting Gram-negative bacteria.

Gram-negative bacteria are more resistant to many antimicrobial agents than Gram-positive bacteria. This is because drugs must pass through an additional barrier of the outer membrane in order to access the cytoplasmic membrane or the interior of the cell. In spite of this fact, the presence of the outer membrane also provides an alternative target for the action of antimicrobial agents. In addition, the cytoplasmic membranes of Gram-negative bacteria are generally more enriched with the phospholipid phosphatidylethanolamine than those of Gram-positive bacteria. In this chapter, we outline novel strategies for using the interaction of antimicrobial agents with components of the membranes of Gramnegative bacteria in order to design agents that have a higher toxicity for these bacteria.