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

    Year: 2022

    Journal: ACS Infect. Dis., Volume 8, SEP 9, page 1823–1830

    Authors: Lin, Jennifer S.; Bekale, Laurent A.; Molchanova, Natalia; Nielsen, Josefine Eilso; Wright, Megan; Bacacao, Brian; Diamond, Gill; Jenssen, Havard; Santa Maria, Peter L.; Barron, Annelise E.

    Organizations: Stanford's SPARK Translational Research Program; Stanford Maternal and Child Health Research Institute (MCHRI); NIH/NIA [1DP1OD029517-01]; DOE Office of Biological and Environmental Research; National Institutes of Health [P30 GM124169, S10OD018483]; Office of Science, Office of Basic Energy Sciences, of the U.S. DOE [DE-AC02-05CH11231]

    Keywords: peptoids; micelles; antibacterial; biofilm; persister cells

    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 predinical 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 TMS, is active against planktonic persister cells and sterilizes biofilms formed by both Gram-negative and Grampositive bacteria. Moreover, we demonstrate the potential of TMS 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.
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