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Histones from Avian Erythrocytes Exhibit Antibiofilm activity against methicillin-sensitive and methicillin-resistant
Megan Rose-Martel1, Garima Kulshreshtha1, Nahom Ahferom Berhane1
1Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, K1H 8M5 Canada.
Abstract:
Staphylococcus aureus, a human pathogen associated with many illnesses and post-surgical infections, can resist treatment due to the emergence of antibiotic-resistant strains and through biofilm formation. The current treatments for chronic biofilm infections are antibiotics and/or surgical removal of the contaminated medical device. Due to higher morbidity and mortality rates associated with overuse/misuse of antibiotics, alternate treatments are essential. This study reports the antibiofilm activity of avian erythrocyte histones against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Fluorescence and scanning electron microscopy revealed membrane damage to bacteria in histone-treated biofilms. Histones and indolicidin (positive control) increased the expression of apsS and apsR, which are associated with the Antimicrobial Peptide (AMP) sensor/regulator system in S. aureus. The expression of dltB, and vraF, associated with AMP resistance mechanisms, were under histone inducible control in the biofilm-embedded bacterial cells. The time kill kinetics for histones against S. aureus revealed a rapid biocidal activity (<5 min). Purified erythrocyte-specific histone H5 possessed 3-4 fold enhanced antimicrobial activity against planktonic cells compared to the histone mixture (H1, H2A, H2B, H3, H4, H5). These results demonstrate the promise of histones and histone-like derivatives as novel antibiotics against pathogens in their planktonic and biofilm forms.
Insights
Avian erythrocyte histones show potent antibiofilm activity against Staphylococcus aureus, including antibiotic-resistant strains. These histones damage bacterial membranes and offer a promising alternative to conventional antibiotics for treating persistent infections.
Area of Science:
- Microbiology
- Antimicrobial Research
- Biochemistry
Background:
- Staphylococcus aureus infections pose significant challenges due to antibiotic resistance and biofilm formation.
- Current treatments for chronic S. aureus biofilm infections, including antibiotics and surgery, have limitations and risks.
- The need for novel therapeutic strategies against resistant bacterial pathogens is critical.
Purpose of the Study:
- To investigate the antibiofilm activity of avian erythrocyte histones against Staphylococcus aureus.
- To evaluate the efficacy of histones against both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains.
- To explore the mechanism of action of histones on bacterial membranes and resistance pathways.
Main Methods:
- Treatment of S. aureus biofilms with avian erythrocyte histones.
- Fluorescence and scanning electron microscopy to assess bacterial membrane integrity.
- Gene expression analysis of key S. aureus regulatory systems (apsS, apsR, dltB, vraF) and time-kill kinetics.
Main Results:
- Histones induced significant membrane damage in S. aureus biofilms.
- Histones modulated the expression of genes involved in the Antimicrobial Peptide (AMP) sensor/regulator system and AMP resistance.
- Rapid biocidal activity (<5 min) was observed, with histone H5 showing enhanced efficacy against planktonic cells.
Conclusions:
- Avian erythrocyte histones exhibit potent antibiofilm and antimicrobial activity against S. aureus.
- Histones represent a promising novel therapeutic class for combating planktonic and biofilm-associated S. aureus infections.
- Histone-like derivatives could serve as valuable alternatives to conventional antibiotics.