Redman Whitni K, Welch Garrett S, Williams Avery C, Damron Addyson J, Northcut Willem O, Rumbaugh Kendra P
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Biofilm. 2021 Nov 13;3:100061. doi: 10.1016/j.bioflm.2021.100061. eCollection 2021 Dec.
Novel anti-biofilm and dispersal agents are currently being investigated in an attempt to combat biofilm-associated wound infections. Glycoside hydrolases (GHs) are enzymes that hydrolyze the glycosidic bonds between sugars, such as those found within the exopolysaccharides of the biofilm matrix. Previous studies have shown that GHs can weaken the matrix, inducing bacterial dispersal, and improving antibiotic clearance. Yet, the number of GH enzymes that have been examined for potential therapeutic effects is limited. In this study, we screened sixteen GHs for their ability to disperse mono-microbial and polymicrobial biofilms grown in different environments. Six GHs, α-amylase (source: ), alginate lyase (source: various algae), pectinase (source: Rhizopus sp.), amyloglucosidase (source: inulinase (source: ), and xylanase (source: ), exhibited the highest dispersal efficacy . Two GHs, α-amylase (source: Bacillus sp.) and cellulase (source: ), used in conjunction with meropenem demonstrated infection clearing ability in a mouse wound model. GHs were also effective in improving antibiotic clearance in diabetic mice. To examine their safety, we screened the GHs for toxicity in cell culture. Overall, there was an inverse relationship between enzyme exposure time and cellular toxicity, with twelve out of sixteen GHs demonstrating some level of toxicity in cell culture. However, only one GH exhibited harmful effects in mice. These results further support the ability of GHs to improve antibiotic clearance of biofilm-associated infections and help lay a foundation for establishing GHs as therapeutic agents for chronic wound infections.
目前正在研究新型抗生物膜和分散剂，以对抗与生物膜相关的伤口感染。糖苷水解酶（GHs）是一种能水解糖之间糖苷键的酶，比如在生物膜基质胞外多糖中发现的那些糖苷键。先前的研究表明，GHs可以削弱基质，诱导细菌分散，并提高抗生素清除率。然而，已被研究其潜在治疗效果的GH酶数量有限。在本研究中，我们筛选了16种GHs，以考察它们分散在不同环境中生长的单一微生物和多微生物生物膜的能力。六种GHs，即α-淀粉酶（来源： ）、海藻酸裂合酶（来源：多种藻类）、果胶酶（来源：根霉属）、淀粉葡萄糖苷酶（来源： ）、菊粉酶（来源： ）和木聚糖酶（来源： ），表现出最高的分散效果。两种GHs，即α-淀粉酶（来源：芽孢杆菌属）和纤维素酶（来源： ），与美罗培南联合使用时，在小鼠伤口模型中显示出清除感染的能力。GHs在改善糖尿病小鼠的抗生素清除方面也很有效。为了检测它们的安全性，我们在细胞培养中筛选了GHs的毒性。总体而言，酶暴露时间与细胞毒性之间呈负相关，16种GHs中有12种在细胞培养中表现出一定程度的毒性。然而，只有一种GH在小鼠中表现出有害作用。这些结果进一步支持了GHs改善生物膜相关感染抗生素清除率的能力，并有助于为将GHs确立为慢性伤口感染的治疗药物奠定基础。
