A Study with Peptide Dendrimers Reveals an Extreme pH Dependence of Antibiotic Activity Above pH 7.4

16 March 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

In our efforts to develop peptide dendrimers as a new class of antimicrobial peptides (AMPs) against Gram-negative bacteria, we investigated their activity at acidic and basic pH, which correspond to the conditions of the site of bacterial infections on skin or biofilms and chronic wounds respectively. Removing the eight low pKa amino termini of our reference dendrimer G3KL by substituting the N-terminal lysine residues with aminohexanoic acid provided dendrimer XC1 with a broader pH-activity range. Furthermore, raising the pH to 8.0 revealed strong activities against Klebsiella pneumoniae and methicillin resistant Staphylococcus aureus (MRSA) against which the dendrimers are inactive at pH 7.4, an effect which we also observed with polymyxin B and tentatively assign to stronger binding to the bacteria at higher pH as observed with a fluorescence labeled dendrimer analog.

Keywords

dendrimers
antimicrobial peptides
polymyxin b
antibiotics
peptide dendrimers

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.