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.
Highlights
Staphylococcus aureus is a major human pathogen associated with a range of illnesses, from minor skin infections to life-threatening diseases, such as pneumonia, meningitis, endocarditis, toxic shock syndrome (TSS), bacteremia, and sepsis[1]
We have previously demonstrated that chicken erythrocyte histones exhibit antimicrobial activity towards a variety of Gram-positive and Gram-negative planktonic bacteria, and bind to bacterial cell wall components such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA)[18]
Environmental cues from within an established biofilm can activate dispersal mechanisms, in which some bacteria revert to the planktonic state and are shed from the biofilm to cause acute infections, including sepsis, or form new biofilms at secondary sites leading to chronic infection
Summary
Staphylococcus aureus is a major human pathogen associated with a range of illnesses, from minor skin infections to life-threatening diseases, such as pneumonia, meningitis, endocarditis, toxic shock syndrome (TSS), bacteremia, and sepsis[1]. Cationic antimicrobial peptides (CAMPs), such as cathelicidins, magainins and dermaseptins, are crucial members of the innate immune system. They possess hydrophobic residues, have an overall positive charge and can form amphipathic α-helical structures, ß-sheet structures or remain in a linear arrangement in a membrane-like milieu[8]. Bind to the anionic constituents of the bacterial cell membrane, which pathogens cannot mutate This enables CAMPs to avoid the common resistance mechanisms observed for classical antibiotics[9]. We have previously demonstrated that chicken erythrocyte histones exhibit antimicrobial activity towards a variety of Gram-positive and Gram-negative planktonic bacteria, and bind to bacterial cell wall components such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA)[18]. Mammalian red blood cell membranes were stable to chicken histones treatment and showed no hemolysis even at the highest concentration tested[18]
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