Research output: Contribution to journal › Article › Academic › peer-review
Thrombocidin-1-derived antimicrobial peptide TC19 combats superficial multi-drug resistant bacterial wound infections. / Riool, Martijn; de Breij, Anna; Kwakman, Paulus H. S. et al.
In: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, Vol. 1862, No. 8, 183282, 01.08.2020.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Thrombocidin-1-derived antimicrobial peptide TC19 combats superficial multi-drug resistant bacterial wound infections
AU - Riool, Martijn
AU - de Breij, Anna
AU - Kwakman, Paulus H. S.
AU - Schonkeren-Ravensbergen, Elisabeth
AU - de Boer, Leonie
AU - Cordfunke, Robert A.
AU - Malanovic, Nermina
AU - Drijfhout, Jan W.
AU - Nibbering, Peter H.
AU - Zaat, Sebastian A. J.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Antimicrobial peptides are considered promising candidates for the development of novel antimicrobial agents to combat infections by multi-drug-resistant (MDR) bacteria. Here, we describe the identification and characterization of the synthetic peptide TC19, derived from the human thrombocidin-1-derived peptide L3. Biophysical experiments into the interaction between TC19 and mimics of human and bacterial plasma membranes demonstrated that the peptide is highly selective for bacterial membranes. In agreement, TC19 combined low cytotoxicity towards human fibroblasts with efficient and rapid killing in human plasma of MDR strains of several bacterial species of the ESKAPE panel. In addition, TC19 induced minor resistance in vitro, neutralized pro-inflammatory activity of bacterial cell envelope components while displaying slight chemotactic activity for human neutrophils. Importantly, topical application of TC19-containing hypromellose gel significantly reduced numbers of viable methicillin-resistant Staphylococcus aureus (MRSA) and MDR Acinetobacter baumannii in a superficial wound infection in mice. Together, TC19 is an attractive candidate for further development as a novel agent against (MDR) bacterial skin wound infections.
AB - Antimicrobial peptides are considered promising candidates for the development of novel antimicrobial agents to combat infections by multi-drug-resistant (MDR) bacteria. Here, we describe the identification and characterization of the synthetic peptide TC19, derived from the human thrombocidin-1-derived peptide L3. Biophysical experiments into the interaction between TC19 and mimics of human and bacterial plasma membranes demonstrated that the peptide is highly selective for bacterial membranes. In agreement, TC19 combined low cytotoxicity towards human fibroblasts with efficient and rapid killing in human plasma of MDR strains of several bacterial species of the ESKAPE panel. In addition, TC19 induced minor resistance in vitro, neutralized pro-inflammatory activity of bacterial cell envelope components while displaying slight chemotactic activity for human neutrophils. Importantly, topical application of TC19-containing hypromellose gel significantly reduced numbers of viable methicillin-resistant Staphylococcus aureus (MRSA) and MDR Acinetobacter baumannii in a superficial wound infection in mice. Together, TC19 is an attractive candidate for further development as a novel agent against (MDR) bacterial skin wound infections.
KW - Antibacterial activity
KW - Thrombocidin-derived peptide
KW - Wound infection
UR - http://www.scopus.com/inward/record.url?scp=85084416277&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2020.183282
DO - 10.1016/j.bbamem.2020.183282
M3 - Article
C2 - 32376222
VL - 1862
JO - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
SN - 0005-2736
IS - 8
M1 - 183282
ER -
ID: 11609013