Naturally derived peptides enhance killing efficiency of colistin against colistin-resistant bacteria
Primary author: Kaitlin Witherell
Faculty sponsor: Dr. Douglas Call
Primary college/unit: College of Veterinary Medicine
Colistin is a “last-line” antibiotic that is used to treat multidrug-resistant, Gram-negative bacteria, but colistin resistance has emerged. In susceptible bacteria, colistin binds lipid A and destroys the bacterial membrane. MCR (encoded by mcr-1 and others) is a phosphoethanolamine transferase that modifies lipid A resulting in decreased affinity for colistin. We are investigating two cysteine-dense peptides (CDPs), “B03” and “B11” that appear to kill bacteria by interacting with the bacterial membrane. We propose that using CDPs in combination with colistin we can kill colistin- and multidrug-resistant bacteria at lower concentrations and more quickly compared to colistin alone. We have shown B03 and B11 are able to reduce the colistin resistance profile of mcr-1 harboring and multidrug-resistant Escherichia coli AR Bank #0346. By adding 100 µg/ml of peptide B03 we are able to significantly reduce the minimum inhibitory concentration (MIC) of colistin from 1.25 µg/ml to 0.063 µg/ml. When 50 µg/ml of peptide B11 is added the MIC of colistin is reduced to less than 0.0005 µg/ml. We also found that by adding either peptide, 346 is killed faster and at lower concentrations compared to using colistin alone. We are determining the mechanism of action of these peptides by performing membrane potential assays and employing scanning electron microscopy.