Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; School of Medicine, Tongji University, Shanghai 200092, China.
Sci Total Environ. 2022 Feb 10;807(Pt 3):151855. doi: 10.1016/j.scitotenv.2021.151855. Epub 2021 Nov 20.
Biofilm formation is an important factor for Mycobacterium abscessus to resist harsh environment and produce drug resistance. The anti-biofilm activity of a newly designed antibacterial peptide, RP557, was investigated. The effect of RP557 alone or in combination with several clinically effective antibiotics, including clarithromycin, amikacin, cefoxitin and imipenem, on M. abscessus growth in biofilms was determined. Microstructural changes in biofilms after RP557 treatment were observed by scanning electron microscope. The effect of RP557 on the viability of bacteria was determined by Syto9/PI staining and fluorescence microscopy. Finally, the potential mechanism of RP557 action on biofilm development was explored by transcriptome analysis. M. abscessus growing in biofilms showed increased resistance to antimicrobial drugs. RP557 alone exhibited only moderate anti-M. abscessus activity in vitro, but significantly increased the antibiotic sensitivity of M. abscessus in biofilms. The inhibitory effect of RP557 on biofilm formation was visualized by the scanning electron microscope; fluorescence staining demonstrated increased bacterial death in response to RP557 treatment. Furthermore, comparative analysis of transcriptomic data suggested RP557 may inhibit biofilm formation by down-regulating nitrogen and fatty acid metabolism, as well as peptidoglycan biosynthesis. As such, RP557 is a potential candidate to include in novel strategies to treat M. abscessus infections.
生物膜形成是脓肿分枝杆菌抵抗恶劣环境和产生耐药性的重要因素。本研究旨在探究一种新设计的抗菌肽 RP557 的抗生物膜活性。单独使用 RP557 或联合几种临床有效抗生素（克拉霉素、阿米卡星、头孢西丁和亚胺培南）对生物膜中脓肿分枝杆菌生长的影响。通过扫描电子显微镜观察 RP557 处理后生物膜的微观结构变化。通过 Syto9/PI 染色和荧光显微镜观察 RP557 对细菌活力的影响。最后，通过转录组分析探讨 RP557 对生物膜发育作用的潜在机制。在生物膜中生长的脓肿分枝杆菌对抗菌药物的耐药性增加。RP557 单独使用时，体外对脓肿分枝杆菌的抗菌活性仅为中度，但显著增加了生物膜中脓肿分枝杆菌对抗生素的敏感性。扫描电子显微镜观察到 RP557 对生物膜形成的抑制作用；荧光染色显示，细菌死亡增加。此外，转录组数据的比较分析表明，RP557 可能通过下调氮和脂肪酸代谢以及肽聚糖生物合成来抑制生物膜形成。因此，RP557 可能是治疗脓肿分枝杆菌感染的新策略的潜在候选药物。
