Merck

Efficacy and safety of biofilm dispersal by glycoside hydrolases in wounds.

Biofilm (2021-11-27)
Whitni K Redman, Garrett S Welch, Avery C Williams, Addyson J Damron, Willem O Northcut, Kendra P Rumbaugh
要旨

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: A. oryzae), alginate lyase (source: various algae), pectinase (source: Rhizopus sp.), amyloglucosidase (source: A. niger), inulinase (source: A. niger), and xylanase (source: A. oryzae), exhibited the highest dispersal efficacy in vitro. Two GHs, α-amylase (source: Bacillus sp.) and cellulase (source: A. niger), 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.

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製品内容

Sigma-Aldrich
アルギン酸リアーゼ from Flavobacterium multivorum, powder, ≥10,000 units/g solid
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α-アミラーゼ from Aspergillus oryzae, ≥150 units/mg protein (biuret)
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キシラナーゼ Thermomyces lanuginosus由来, powder, ≥2500 units/g, recombinant, expressed in Aspergillus oryzae
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ペクチナーゼ from Rhizopus sp., powder, 400-800 units/g solid
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アミログルコシダーゼ from Aspergillus niger, powder, white, ~120 U/mg
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アミログルコシダーゼ from Rhizopus sp., ≥40,000 units/g solid
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β-アミラーゼ from barley, Type II-B, 20-80 units/mg protein (biuret)
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α-アミラーゼ ブタ膵臓由来, Type I-A, PMSF treated, saline suspension, 700-1400 units/mg protein (E1%/280)
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ペクチナーゼ from Aspergillus niger, powder, slightly beige, >1 U/mg
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イヌリナーゼ from Aspergillus niger, lyophilized, powder, brown-gray, ~25 U/mg