Antibiofilm Activity and Synergistic Inhibition of Staphylococcus aureus Biofilms by Bactericidal Protein P128 in Combination with Antibiotics
Antibiofilm Activity and Synergistic Inhibition of Staphylococcus aureus Biofilms by Bactericidal Protein P128 in Combination with Antibiotics
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DOI：
10.1128/aac.01118-16
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发表时间：
2016-12-01
影响因子：
4.9
通讯作者：
Sharma, Umender
中科院分区：
文献类型：
--
作者：
Nair, Sandhya;Desai, Srividya;Sharma, Umender
P128是一种抗葡萄球菌蛋白，包括细胞壁降解酶区域和葡萄球菌特异性结合区域，其对敏感和耐药金黄色葡萄球菌菌株具有特异性和有效的杀菌活性。探讨P128对S.在与临床感染相关的一系列环境中，我们研究了抗金黄色葡萄球菌。图4显示了单独的P128和与标准护理抗生素组合的P128对牙周炎和生物膜包埋的细胞的金黄色葡萄球菌活性。P128对S.通过CFU减少和比色最小生物膜抑制浓度（MBIC）测定检测金黄色葡萄球菌生物膜。微滴定板和导管表面生物膜的扫描电镜图像显示，低浓度的P128可破坏生物膜结构并裂解细胞。当它与抗生素联合使用时，已知抗生素是S。在生物膜中的金黄色葡萄球菌，如万古霉素、庆大霉素、环丙沙星、利奈唑胺和达托霉素中，P128显示出高度协同的生物膜活性，这导致P128和各个抗生素的MBIC值大大降低。敏感株和耐药株均表现出协同作用。金黄色的此外，在模拟伤口感染环境的体外混合生物膜模型中，P128能够凭借其抗葡萄球菌活性防止生物膜形成。强大的S。P128单独和与抗生素组合的金黄色葡萄球菌生物膜抑制活性是P128用于治疗复杂的金黄色葡萄球菌的发展的令人鼓舞的迹象。涉及生物膜的金黄色葡萄球菌感染。
P128 is an antistaphylococcal protein, comprising a cell wall-degrading enzymatic region and a Staphylococcus-specific binding region, which possesses specific and potent bactericidal activity against sensitive and drug-resistant strains of Staphylococcus aureus. To explore P128's ability to kill S. aureus in a range of environments relevant to clinical infection, we investigated the anti-S. aureus activity of P128 alone and in combination with standard-of-care antibiotics on planktonic and biofilm-embedded cells. P128 was found to have potent antibiofilm activity on preformed S. aureus biofilms as detected by CFU reduction and a colorimetric minimum biofilm inhibitory concentration (MBIC) assay. Scanning electron microscopic images of biofilms formed on the surfaces of microtiter plates and on catheters showed that P128 at low concentrations could destroy the biofilm structure and lyse the cells. When it was tested in combination with antibiotics which are known to be poor inhibitors of S. aureus in biofilms, such as vancomycin, gentamicin, ciprofloxacin, linezolid, and daptomycin, P128 showed highly synergistic antibiofilm activity that resulted in much reduced MBIC values for P128 and the individual antibiotics. The synergistic effect was seen for both sensitive and resistant isolates of S. aureus. Additionally, in an in vitro mixed-biofilm model mimicking the wound infection environment, P128 was able to prevent biofilm formation by virtue of its anti-Staphylococcus activity. The potent S. aureus biofilm-inhibiting activity of P128 both alone and in combination with antibiotics is an encouraging sign for the development of P128 for treatment of complicated S. aureus infections involving biofilms.