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.
Sci Rep. 2017 Apr 5;7:45980. doi: 10.1038/srep45980.
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.
金黄色葡萄球菌是一种与许多疾病和术后感染有关的人类病原体，由于抗生素耐药菌株的出现和生物膜的形成，它可以抵抗治疗。目前治疗慢性生物膜感染的方法是使用抗生素和/或手术切除受污染的医疗器械。由于抗生素过度使用/误用导致的发病率和死亡率更高，因此需要替代治疗方法。本研究报告了禽红细胞组蛋白对甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）的抗生物膜活性。荧光和扫描电子显微镜显示，组蛋白处理的生物膜中的细菌的细胞膜受到了损伤。组蛋白和吲哚丁素（阳性对照）增加了 apsS 和 apsR 的表达，这与金黄色葡萄球菌中的抗菌肽（AMP）传感器/调节系统有关。与 AMP 耐药机制相关的 dltB 和 vraF 的表达受生物膜中细菌细胞中组蛋白的诱导控制。组蛋白对金黄色葡萄球菌的时间杀伤动力学研究表明，其具有快速杀菌活性（<5 分钟）。与组蛋白混合物（H1、H2A、H2B、H3、H4、H5）相比，纯化的红细胞特异性组蛋白 H5 对浮游细胞的抗菌活性增强了 3-4 倍。这些结果表明组蛋白和组蛋白类似物作为新型抗生素，具有针对浮游生物和生物膜形式的病原体的应用潜力。
