Anti-persister and Anti-biofilm Activity of Self-Assembled Antimicrobial Peptoid Ellipsoidal Micelles

• Published in: ACS infectious diseases Vol. 8; no. 9; pp. 1823 - 1830
• Main Authors: Lin, Jennifer S., Bekale, Laurent A., Molchanova, Natalia, Nielsen, Josefine Eilsø, Wright, Megan, Bacacao, Brian, Diamond, Gill, Jenssen, Håvard, Santa Maria, Peter L., Barron, Annelise E.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 09.09.2022
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - pharmacology; antibacterial; antimicrobial agents; bacteria; biofilm; biofilms; Humans; infectious diseases; Letter; Micelles; Microbial Sensitivity Tests; peptides and proteins; peptoids; Peptoids - pharmacology; persister cells; Recurrence; antibacterial; peptoids; micelles; biofilm; persister cells
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.2c00288

Although persister cells are the root cause of resistance development and relapse of chronic infections, more attention has been focused on developing antimicrobial agents against resistant bacterial strains than on developing anti-persister agents. Frustratingly, the global preclinical antibacterial pipeline does not include any anti-persister drug. Therefore, the central point of this work is to explore antimicrobial peptidomimetics called peptoids (sequence-specific oligo-N-substituted glycines) as a new class of anti-persister drugs. In this study, we demonstrate that one particular antimicrobial peptoid, the sequence-specific pentamer TM5, is active against planktonic persister cells and sterilizes biofilms formed by both Gram-negative and Gram-positive bacteria. Moreover, we demonstrate the potential of TM5 to inhibit cytokine production induced by lipopolysaccharides from Gram-negative bacteria. We anticipate that this work can pave the way to the development of new anti-persister agents based on antimicrobial peptoids of this class to simultaneously help address the crisis of bacterial resistance and reduce the occurrence of the relapse of chronic infections.