Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci.

Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci.
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DOI:
10.1038/ja.2011.113
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发表时间:
2012-02
期刊:
The Journal of antibiotics
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其他
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细胞外DNA是葡萄球菌生物膜的粘附成分。本研究的目的是评价重组人dna酶I (rhDNase)对金黄色葡萄球菌和表皮葡萄球菌的抗菌活性。通过96孔微滴板结晶紫结合实验,我们发现1 ~ 4 μg l−1的rhDNase能有效抑制金黄色葡萄球菌生物膜的形成,1 mg l−1的rhDNase能在2 min内有效分离金黄色葡萄球菌生物膜。用10 mg l−1 rhDNase预处理金黄色葡萄球菌生物膜10分钟,可使其对杀菌剂的敏感性提高4-5 log单位。rhDNase在10 mg l−1的培养基中显著抑制表皮葡萄球菌形成生物膜,培养基中添加了亚最低抑制浓度的抗生素。我们还发现,与单独使用妥布霉素处理的线虫相比,rhDNase显著提高了金黄色葡萄球菌感染的秀丽隐杆线虫的存活率。我们得出结论,在临床可达到的浓度下,rhDNase对金黄色葡萄球菌和表皮葡萄球菌表现出有效的抗生素膜和抗菌增敏活性。rhDNase,无论是单独使用还是与抗菌剂联合使用,都可能在治疗或预防葡萄球菌生物膜相关感染方面有应用。
Extracellular DNA is an adhesive component of staphylococcal biofilms. The aim of this study was to evaluate the antibiofilm activity of recombinant human DNase I (rhDNase) against Staphylococcus aureus and Staphylococcus epidermidis. Using a 96-well microtiter plate crystal violet binding assay, we found that biofilm formation by S. aureus was efficiently inhibited by rhDNase at 1–4 μg l−1, and pre-formed S. aureus biofilms were efficiently detached in 2 min by rhDNase at 1 mg l−1. Pre-treatment of S. aureus biofilms for 10 min with 10 mg l−1 rhDNase increased their sensitivity to biocide killing by 4–5 log units. rhDNase at 10 mg l−1 significantly inhibited biofilm formation by S. epidermidis in medium supplemented with subminimal inhibitory concentrations of antibiotics. We also also found rhDNase significantly increased the survival of S. aureus-infected C. elegans nematodes treated with tobramycin compared to nematodes treated with tobramycin alone. We concluded that rhDNase exhibits potent antibiofilm and antimicrobial-sensitizing activities against S. aureus and S. epidermidis at clinically achievable concentrations. rhDNase, either alone or in combination with antimicrobial agents, may have applications in treating or preventing staphylococcal biofilm-related infections.
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