Modulation of antimicrobial potency of human cathelicidin peptides against the ESKAPE pathogens and in vivo efficacy in a murine catheter-associated biofilm model

Jayaram Lakshmaiah Narayana, Biswajit Mishra, Tamara Lushnikova, Radha M. Golla, Guangshun Wang

Research output: Contribution to journalArticle

Abstract

Antimicrobial peptides are essential components of innate immune systems that protect hosts from infection. They are also useful candidates for developing a new generation of antibiotics to fight antibiotic-resistant pathogens. Human innate immune peptide LL-37 can inhibit biofilm formation, but suffers from high cost due to a long peptide length and rapid protease degradation. To improve the peptide, we previously identified the major active region and changed the peptide backbone structure. This study designed two families of new peptides by altering peptide side chains. Interestingly, these peptides displayed differential potency against various ESKAPE pathogens in vitro and substantially reduced hemolysis. Further potency test in vivo revealed that 17tF-W eliminated the burden of methicillin-resistant Staphylococcus aureus (MRSA) USA300 in both mouse-embedded catheters and their surrounding tissues. In addition, peptide treatment suppressed the level of chemokine TNFα, and boosted the levels of chemokines MCP-1, IL-17A and IL-10 in the surrounding tissues of the infected catheter embedded in mice. In conclusion, we have designed a set of new LL-37 peptides with varying antimicrobial activities, opening the door to potential topical treatment of infections involving different drug-resistant pathogens.

Original languageEnglish (US)
Pages (from-to)1592-1602
Number of pages11
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Issue number9
DOIs
StatePublished - Sep 1 2019

Fingerprint

Catheters
Biofilms
Pathogens
Modulation
Peptides
Chemokines
Tissue
Anti-Bacterial Agents
Methicillin
Interleukin-17
cathelicidin antimicrobial peptide
Immune system
Methicillin-Resistant Staphylococcus aureus
Hemolysis
Infection
Interleukin-10
Immune System
Peptide Hydrolases
Costs and Cost Analysis
Degradation

Keywords

  • Biofilms
  • Cathelicidin
  • Catheter
  • Cytotoxicity
  • LL-37
  • Peptide design

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Modulation of antimicrobial potency of human cathelicidin peptides against the ESKAPE pathogens and in vivo efficacy in a murine catheter-associated biofilm model. / Narayana, Jayaram Lakshmaiah; Mishra, Biswajit; Lushnikova, Tamara; Golla, Radha M.; Wang, Guangshun.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1861, No. 9, 01.09.2019, p. 1592-1602.

Research output: Contribution to journalArticle

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