Abstract
Modern medicine is challenged continuously by the increasing prevalence of antibiotic resistant bacteria. Cationic antimicrobial peptides and their derivatives are interesting potential alternatives to antibiotics due to their rapid action, broad-spectrum of antimicrobial activity and limited emergence of bacterial resistance. This study reports the novel antimicrobial properties of histone H5, purified from chicken erythrocytes, and histone H5-derived synthetic peptides. Broth microdilution assays revealed that histone H5 has potent broad-spectrum antimicrobial activity against Gram-positive and Gram-negative planktonic bacteria (MIC range: 1.9 ± 1.8 to 4.9 ± 1.5 µg/mL), including vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, histone H5 displayed anti-biofilm activity against established Listeria monocytogenes and Pseudomonas aeruginosa biofilms. Scanning electron microscopy demonstrated bacterial membrane damage after histone H5 treatment, while a hemolytic assay revealed that histone H5 is non-toxic towards mammalian erythrocytes, even at a concentration of 1 mg/mL. Although the predicted H5-derived antimicrobial peptides tested in this study were located within the antimicrobial domain of histone H5, their synthetic versions did not possess more potent antimicrobial activity than the full length protein. Overall, this study demonstrates that histone H5 is a potent antimicrobial and therefore a promising template for the development of novel histone H5-derived antimicrobial peptides.
Highlights
The discovery of antibiotics has greatly changed global health by effectively treating bacterial infections
Development of resistance to Cationic antimicrobial peptides (CAMPs) by bacteria is limited compared to that observed against antibiotics, such antimicrobial peptides have been acting upon bacteria for hundreds of millions of years18,19
Due to their broad-spectrum of antimicrobial activity and membrane-dependent mechanism of action, CAMPs and CAMP-derivatives are interesting candidates to overcome the global threat of antibiotic resistance
Summary
The discovery of antibiotics has greatly changed global health by effectively treating bacterial infections. The use of natural CAMPs as therapeutic agents has been widely investigated in recent years; high manufacturing costs have been a major barrier to their widespread use. The use of natural CAMPs as therapeutic agents has been widely investigated in recent years; high manufacturing costs have been a major barrier to their widespread use20 To address this issue, the identification of shorter peptides based upon the hydrophobicity, charge and amino acid composition of natural CAMPs is an effective strategy. The identification of shorter peptides based upon the hydrophobicity, charge and amino acid composition of natural CAMPs is an effective strategy20,21 Due to their broad-spectrum of antimicrobial activity and membrane-dependent mechanism of action, CAMPs and CAMP-derivatives are interesting candidates to overcome the global threat of antibiotic resistance
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