Peptide Stability Is Important but Not a General Requirement for Antimicrobial and Antibiofilm Activity in Vitro and in Vivo

Aaron P. Decker, Yajuan Su, Biswajit Mishra, Atul Verma, Tamara Lushnikova, Jingwei Xie, Guangshun Wang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Peptide stability to proteases has been a major requirement for developing peptide therapeutics. This study investigates the effects of peptide stability on antimicrobial and antibiofilm activity under various conditions. For this purpose, two human cathelicidin-derived peptides differing in stability to proteases were utilized. While GF-17, a peptide derived from the major antimicrobial region of human LL-37, can be rapidly cleaved by proteases, the engineered peptide 17BIPHE2 is resistant to multiple proteases. In the standard antimicrobial susceptibility, killing kinetics, and membrane permeabilization assays conducted in vitro using planktonic bacteria, these two peptides displayed similar potency. The two peptides were also similarly active against methicillin-resistant Staphylococcus aureus (MRSA) USA300 prior to biofilm formation. However, 17BIPHE2 was superior to GF-17 in disrupting preformed biofilms probably due to both enhanced stability and slightly higher DNA binding capacity. In a wax moth model, 17BIPHE2 better protected insects from MRSA infection-caused death than GF-17, consistent with the slower degradation of 17BIPHE2 than GF-17. Here, peptide antimicrobial activity was found to be critical for in vivo efficacy. When incorporated in the nanofiber/microneedle delivery device, GF-17 and 17BIPHE2 displayed a similar effect in eliminating MRSA in murine chronic wounds, underscoring the advantage of nanofibers in protecting the peptide from degradation. Since nanoformulation can ease the requirement of peptide stability, it opens the door to a direct use of natural peptides or their cocktails for antimicrobial treatment, accelerating the search of effective antibiofilm peptides to treat chronic wounds.

Original languageEnglish (US)
Pages (from-to)738-749
Number of pages12
JournalMolecular Pharmaceutics
Issue number1
StatePublished - Jan 2 2023


  • LL-37
  • MRSA
  • antimicrobial susceptibility
  • biofilms
  • peptide stability
  • wound healing

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


Dive into the research topics of 'Peptide Stability Is Important but Not a General Requirement for Antimicrobial and Antibiofilm Activity in Vitro and in Vivo'. Together they form a unique fingerprint.

Cite this