title: Histones from Avian Erythrocytes Exhibit Antibiofilm activity against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.
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.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, K1H 8M5 Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: Rose-Martel
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, K1H 8M5 Canada.
authors.forename: Garima
authors.initials: G
authors.lastname: Kulshreshtha
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, K1H 8M5 Canada.
authors.forename: Nahom
authors.initials: N
authors.lastname: Ahferom Berhane
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, K1H 8M5 Canada.
authors.forename: Joelle
authors.initials: J
authors.lastname: Jodoin
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, K1H 8M5 Canada.|Department of Innovation in Medical Education, Faculty of Medicine, University of Ottawa, Ontario, K1H 8M5 Canada.
authors.forename: Maxwell T
authors.initials: MT
authors.lastname: Hincke
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011232:Chemical Precipitation; D002645:Chickens / Q000378:metabolism*; D002853:Chromatography, Liquid; D003720:Densitometry; D004912:Erythrocytes / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000302:isolation & purification / Q000494:pharmacology*; D007700:Kinetics; D008712:Methicillin / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008954:Models, Biological; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D006657:Histones; D012333:RNA, Messenger; D008712:Methicillin