4.6 Article

Engineered peptide PLG0206 overcomes limitations of a challenging antimicrobial drug class

Journal

PLOS ONE
Volume 17, Issue 9, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0274815

Keywords

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Funding

  1. National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS K08AR071494]
  2. National Center for Advancing Translational Science [NCATS KL2TR0001856]
  3. Orthopedic Research and Education Foundation
  4. Musculoskeletal Tissue Foundation
  5. ASPR/BARDA [IDSEP160030]
  6. Wellcome Trust

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The lack of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Researchers have designed PLG0206, an engineered antimicrobial peptide, to overcome the challenges associated with size, toxicity, safety profile, and pharmacokinetics. PLG0206 has demonstrated broad-spectrum antibacterial and anti-biofilm activity, making it a potential treatment for multidrug-resistant pathogens.
The absence of novel antibiotics for drug-resistant and biofilm-associated infections is a global public health crisis. Antimicrobial peptides explored to address this need have encountered significant development challenges associated with size, toxicity, safety profile, and pharmacokinetics. We designed PLG0206, an engineered antimicrobial peptide, to address these limitations. PLG0206 has broad-spectrum activity against >1,200 multidrug-resistant (MDR) ESKAPEE clinical isolates, is rapidly bactericidal, and displays potent anti-biofilm activity against diverse MDR pathogens. PLG0206 displays activity in diverse animal infection models following both systemic (urinary tract infection) and local (prosthetic joint infection) administration. These findings support continuing clinical development of PLG0206 and validate use of rational design for peptide therapeutics to overcome limitations associated with difficult-to-drug pharmaceutical targets.

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