"Doubly Selective" Antimicrobial Polymers: How Do They Differentiate between Bacteria?

We have investigated how doubly selective synthetic mimics of antimicrobial peptides (SMAMPs), which can differentiate not only between bacteria and mammalian cells, but also between Gram‐negative and Gram‐positive bacteria, make the latter distinction. By dye‐leakage experiments on model vesicles and complementary experiments on bacteria, we were able to relate the Gram selectivity to structural differences of these bacteria types. We showed that the double membrane of E. coli rather than the difference in lipid composition between E. coli and S. aureus was responsible for Gram selectivity. The molecular‐weight‐dependent antimicrobial activity of the SMAMPs was shown to be a sieving effect: while the 3000 g mol−1 SMAMP was able to penetrate the peptidoglycan layer of the Gram‐positive S. aureus bacteria, the 50000 g mol−1 SMAMP got stuck and consequently did not have antimicrobial activity. Discriminating tastes: “Doubly selective” antimicrobial polymers differentiate not only between bacteria and the cells of the host organism, but also between Gram‐negative and Gram‐positive bacteria. We rationalize this observation by dye‐leakage studies on model vesicles that mimic E. coli and S. aureus, and complementary experiments with bacteria cells.