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In vitro efficacy of different PEGylation designs on cathelicidin-like peptide with high antibacterial and antifungal activity
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In vitro efficacy of different PEGylation designs on cathelicidin-like peptide with high antibacterial and antifungal activity
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Journal Article
In vitro efficacy of different PEGylation designs on cathelicidin-like peptide with high antibacterial and antifungal activity
2023
Overview
Recent reports on antibiotic resistance have highlighted the need to reduce the impact of this global health issue through urgent prevention and control. The World Health Organization currently considers antibiotic resistance as one of the most dangerous threats to global health. Therefore, Antimicrobial peptides (AMPs) are promising for the development of novel antibiotic molecules due to their high antimicrobial effects, non-inducing antimicrobial resistance (AMR) properties, and broad spectrum. Hence, in this study, we developed novel antimicrobial peptide/polymer conjugates to reduce the adverse effects of TN6 (RLLRLLLRLLR) peptide. We demonstrate how our constructs function in vitro in terms of antimicrobial activity, hemolytic activity, cytotoxicity, and protease resistance. Our findings show that our molecules are effective against different types of microorganisms such as
Staphylococcus aureus
,
Escherichia coli
,
Pseudomonas aeruginosa
, methicillin-resistant
S. aureus
, vancomycin-resistant
Enteroccus faecium
, and
Candida albicans
, which are known to be pathogenic and antibiotic-resistant. Our constructs generally showed low cytotoxicity relative to the peptide in HaCaT and 3T3 cells. Especially these structures are very successful in terms of hemotoxicity. In the bacteremia model with
S. aureus
, the naked peptide (TN6) was hemotoxic even at 1 µg/mL, while the hemotoxicity of the conjugates was considerably lower than the peptide. Remarkably in this model, the hemolytic activity of PepC-PEG-pepC conjugate decreased 15-fold from 2.36 to 31.12 µg/mL compared to the bacteria-free 60-min treatment. This is proof that in the case of bacteremia and sepsis, the conjugates specifically direct to bacterial cell membranes rather than red blood cells. In addition, the PepC-PEG-pepC conjugate is resistant to plasma proteases. Moreover, morphological and intracellular damage of the peptide/conjugates to
Escherichia coli
are demonstrated in SEM and TEM images. These results suggest our molecules can be considered potential next-generation broad-spectrum antibiotic molecule/drug candidates that might be used in clinical cases such as bacteremia and sepsis.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
