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• W3175514168 abstract "Background/Aim: Host defense peptides (HDPs) have the potential to provide a novel solution to antimicrobial resistance (AMR) in view of their unique and broad-spectrum antimicrobial activities. We had recently developed a novel hybrid HDP based on LL-37 and human beta-defensin-2, named CaD23, which was shown to exhibit good in vivo antimicrobial efficacy against Staphylococcus aureus in a bacterial keratitis murine model. This study aimed to examine the potential CaD23-antibiotic synergism and the secondary structure and underlying mechanism of action of CaD23. Methods: Peptide-antibiotic interaction was evaluated against S. aureus, methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa using established checkerboard and time-kill assays. Fractional inhibitory concentration index (FICI) was calculated and interpreted as synergistic (FIC<0.5), additive (FIC between 0.5-1.0), indifferent (FIC between >1.0 and ≤4), or antagonistic (FIC>4). SYTOX green uptake assay was performed to determine the membrane-permeabilising action of CaD23. Molecular dynamics (MD) simulations were performed to evaluate the interaction of CaD23 with bacterial and mammalian mimetic membranes. Circular dichroism (CD) spectroscopy was also performed to examine the secondary structures of CaD23. Results: CaD23-amikacin and CaD23-levofloxacin combination treatment exhibited a strong additive effect against S. aureus SH1000 (FICI = 0.60-0.69) and MRSA43300 (FICI = 0.56-0.60) but an indifferent effect against P. aeruginosa (FIC = 1.03-1.15). CaD23 (at 25 μg/ml; 2xMIC) completely killed S. aureus within 30 min. When used at sub-MIC concentration (3.1 μg/ml; 0.25xMIC), it was able to expedite the antimicrobial action of amikacin against S. aureus by 50%. The rapid antimicrobial action of CaD23 was attributed to the underlying membrane-permeabilising mechanism of action, evidenced by the SYTOX green uptake assay and MD simulations studies. MD simulations revealed that cationicity, alpha-helicity, amphiphilicity and hydrophobicity (related to the Trp residue at C-terminal) play important roles in the antimicrobial action of CaD23. The secondary structures of CaD23 observed in MD simulations were validated by CD spectroscopy. Conclusion: CaD23 is a novel alpha-helical, membrane-active synthetic HDP that can enhance and expedite the antimicrobial action of antibiotics against Gram-positive bacteria when used in combination. MD simulations serves as a powerful tool in revealing the peptide secondary structure, dissecting the mechanism of action, and guiding the design and optimisation of HDPs." @default.
• W3175514168 created "2021-07-05" @default.
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• W3175514168 date "2021-10-07" @default.
• W3175514168 modified "2023-10-16" @default.
• W3175514168 title "Evaluation of Host Defense Peptide (CaD23)-Antibiotic Interaction and Mechanism of Action: Insights From Experimental and Molecular Dynamics Simulations Studies" @default.
• W3175514168 cites W1874122563 @default.
• W3175514168 cites W1976301815 @default.
• W3175514168 cites W1976499671 @default.
• W3175514168 cites W1978498560 @default.
• W3175514168 cites W1978862538 @default.
• W3175514168 cites W1982945317 @default.
• W3175514168 cites W1984563949 @default.
• W3175514168 cites W1987684917 @default.
• W3175514168 cites W1994076503 @default.
• W3175514168 cites W1994349207 @default.
• W3175514168 cites W1997152791 @default.
• W3175514168 cites W2012700578 @default.
• W3175514168 cites W2025938842 @default.
• W3175514168 cites W2035687084 @default.
• W3175514168 cites W2041652966 @default.
• W3175514168 cites W2047145390 @default.
• W3175514168 cites W2082122470 @default.
• W3175514168 cites W2084140416 @default.
• W3175514168 cites W2099028084 @default.
• W3175514168 cites W2100733711 @default.
• W3175514168 cites W2102906662 @default.
• W3175514168 cites W2111078168 @default.
• W3175514168 cites W2118571345 @default.
• W3175514168 cites W2119561943 @default.
• W3175514168 cites W2128572087 @default.
• W3175514168 cites W2132262459 @default.
• W3175514168 cites W2143459609 @default.
• W3175514168 cites W2144048606 @default.
• W3175514168 cites W2169690072 @default.
• W3175514168 cites W2171584190 @default.
• W3175514168 cites W2189116376 @default.
• W3175514168 cites W2206954826 @default.
• W3175514168 cites W2271736303 @default.
• W3175514168 cites W2337957188 @default.
• W3175514168 cites W2342480919 @default.
• W3175514168 cites W2363708275 @default.
• W3175514168 cites W2416290591 @default.
• W3175514168 cites W2552497246 @default.
• W3175514168 cites W2588436517 @default.
• W3175514168 cites W2604779599 @default.
• W3175514168 cites W2612215267 @default.
• W3175514168 cites W2613613983 @default.
• W3175514168 cites W2621208977 @default.
• W3175514168 cites W2752397167 @default.
• W3175514168 cites W2755440815 @default.
• W3175514168 cites W2792192531 @default.
• W3175514168 cites W2794522259 @default.
• W3175514168 cites W2809372875 @default.
• W3175514168 cites W2810412408 @default.
• W3175514168 cites W2887460592 @default.
• W3175514168 cites W2907259115 @default.
• W3175514168 cites W2910431832 @default.
• W3175514168 cites W2914213905 @default.
• W3175514168 cites W2919451909 @default.
• W3175514168 cites W2921685304 @default.
• W3175514168 cites W2943975068 @default.
• W3175514168 cites W2946121773 @default.
• W3175514168 cites W2968517935 @default.
• W3175514168 cites W2972059080 @default.
• W3175514168 cites W2972214861 @default.
• W3175514168 cites W2994287949 @default.
• W3175514168 cites W3005207976 @default.
• W3175514168 cites W3007285729 @default.
• W3175514168 cites W3010656341 @default.
• W3175514168 cites W3015721922 @default.
• W3175514168 cites W3018849032 @default.
• W3175514168 cites W3023849996 @default.
• W3175514168 cites W3027059489 @default.
• W3175514168 cites W3028071381 @default.
• W3175514168 cites W3037402828 @default.
• W3175514168 cites W3091548084 @default.
• W3175514168 cites W3120127585 @default.
• W3175514168 cites W3151637509 @default.
• W3175514168 cites W3156824858 @default.
• W3175514168 cites W3169580339 @default.
• W3175514168 cites W3177309322 @default.
• W3175514168 cites W3186114123 @default.
• W3175514168 cites W3188883555 @default.
• W3175514168 doi "https://doi.org/10.3389/fphar.2021.731499" @default.
• W3175514168 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8528955" @default.
• W3175514168 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34690770" @default.
• W3175514168 hasPublicationYear "2021" @default.
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