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Open AccessArticle

Novel Cecropin-4 Derived Peptides against Methicillin-Resistant Staphylococcus aureus

1
Infectious Diseases Division, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
2
Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China
*
Author to whom correspondence should be addressed.
Both the authors have contributed equally.
Antibiotics 2021, 10(1), 36; https://doi.org/10.3390/antibiotics10010036
Received: 10 December 2020 / Revised: 26 December 2020 / Accepted: 28 December 2020 / Published: 1 January 2021
(This article belongs to the Special Issue Mechanisms of Antimicrobial Peptides on Pathogens)
Increasing microbial resistance, coupled with a lack of new antimicrobial discovery, has led researchers to refocus on antimicrobial peptides (AMPs) as novel therapeutic candidates. Significantly, the less toxic cecropins have gained widespread attention for potential antibacterial agent development. However, the narrow activity spectrum and long sequence remain the primary limitations of this approach. In this study, we truncated and modified cecropin 4 (41 amino acids) by varying the charge and hydrophobicity balance to obtain smaller AMPs. The derivative peptide C18 (16 amino acids) demonstrated high antibacterial activity against Gram-negative and Gram-positive bacteria, as well as yeasts. Moreover, C18 demonstrated a minimal inhibitory concentration (MIC) of 4 µg/mL against the methicillin-resistant Staphylococcus aureus (MRSA) and showed synergy with daptomycin with a fractional inhibition concentration index (FICI) value of 0.313. Similar to traditional cecropins, C18 altered the membrane potential, increased fluidity, and caused membrane breakage at 32 µg/mL. Importantly, C18 eliminated 99% persisters at 10 × MIC within 20 min and reduced the biofilm adherence by ~40% and 35% at 32 and 16 µg/mL. Besides, C18 possessed a strong binding ability with DNA at 7.8 μM and down-regulated the expression of virulence factor genes like agrA, fnb-A, and clf-1 by more than 5-fold (p < 0.05). Interestingly, in the Galleria mellonella model, C18 rescued more than 80% of larva infected with the MRSA throughout 120-h post-infection at a single dose of 8 mg/kg (p < 0.05). In conclusion, this study provides a reference for the transformation of cecropin to derive small peptides and presents C18 as an attractive therapeutic candidate to be developed to treat severe MRSA infections. View Full-Text
Keywords: cecropin; antimicrobial peptides; biofilm; persisters; Staphylococcus aureus cecropin; antimicrobial peptides; biofilm; persisters; Staphylococcus aureus
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MDPI and ACS Style

Peng, J.; Mishra, B.; Khader, R.; Felix, L.; Mylonakis, E. Novel Cecropin-4 Derived Peptides against Methicillin-Resistant Staphylococcus aureus. Antibiotics 2021, 10, 36. https://doi.org/10.3390/antibiotics10010036

AMA Style

Peng J, Mishra B, Khader R, Felix L, Mylonakis E. Novel Cecropin-4 Derived Peptides against Methicillin-Resistant Staphylococcus aureus. Antibiotics. 2021; 10(1):36. https://doi.org/10.3390/antibiotics10010036

Chicago/Turabian Style

Peng, Jian; Mishra, Biswajit; Khader, Rajamohammed; Felix, LewisOscar; Mylonakis, Eleftherios. 2021. "Novel Cecropin-4 Derived Peptides against Methicillin-Resistant Staphylococcus aureus" Antibiotics 10, no. 1: 36. https://doi.org/10.3390/antibiotics10010036

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