Oncotarget

Research Papers:

New antimicrobial peptide kills drug-resistant pathogens without detectable resistance

Jong-Kook Lee, Tudor Luchian and Yoonkyung Park _

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Oncotarget. 2018; 9:15616-15634. https://doi.org/10.18632/oncotarget.24582

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Abstract

Jong-Kook Lee1,3, Tudor Luchian2 and Yoonkyung Park1,3

1Research Center for Proteinaceous Materials, Chosun University, Gwangju, Korea

2Department of Physics, Alexandru I. Cuza University, Iasi, Romania

3Department of Biomedical Science, Chosun University, Gwangju, Korea

Correspondence to:

Yoonkyung Park, email: y_k_park@chosun.ac.kr

Tudor Luchian, email: luchian@uaic.ro

Keywords: Staphylococcus aureus; clavaspirin peptide (CSP); toll-like receptor-2 (TLR-2); nuclear factor-kappa B (NF-κB); pro-inflammatory cytokine

Received: November 03, 2017     Accepted: February 20, 2018     Epub: February 26, 2018     Published: March 20, 2018

ABSTRACT

Clavaspirin peptide (CSP) is derived from the pharyngeal tissues of the tunicate Styela clava. The 23-amino acid peptide is histidine-rich and amidated at the N-terminus. CSP possesses low antimicrobial and high hemolytic activity at pH 7.4. Therefore, we designed 4 CSP analogs with substituted hydrophobic amino acids to reduce hydrophobic amino acid interactions. These modifications reduced the aggregation and cytotoxicity of the analogs at pH 7.4. The analogs also showed potent antimicrobial activity by accumulating on bacterial cell surfaces and inducing the lytic mechanism against gram-negative and gram-positive cells at pH 5.5 and 7.4. Moreover, exposure to the CSP-4 analog for up to 29 passages did not induce drug resistance in Staphylococcus aureus. Application of CSP-4 to inflamed skin of hairless mice infected with drug-resistant S. aureus (DRSA) significantly reduced skin infections without damaging dermal collagen or elastin. Topically applied CSP-4 penetrated 25–40 μm in the dermis within 30 min, reducing the levels of Toll-like receptor-2, nuclear factor kappa B (NF-κB), and the pro-inflammatory cytokines tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1 β). These results suggest that CSP-4 could be a promising topical antimicrobial agent for skin diseases caused by DRSA such as S. aureus CCARM 0027.


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