Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa
Importance of DNase and alginate lyase for enhancing free and liposome encapsulated aminoglycoside activity against Pseudomonas aeruginosa
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DOI：
10.1093/jac/dkp165
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发表时间：
2009-08-01
影响因子：
5.2
通讯作者：
Omri, Abdelwahab
中科院分区：
文献类型：
--
作者：
Alipour, Misagh;Suntres, Zacharias E.;Omri, Abdelwahab
本研究评估了 DNase、藻酸盐裂解酶 (AlgL) 和 N-乙酰半胱氨酸 (NAC) 在增强传统（游离）和囊泡包埋（脂质体）庆大霉素、阿米卡星和妥布霉素的体外杀菌活性方面的潜力。测定了两种铜绿假单胞菌临床分离株（粘液菌株和非粘液菌株）的 MIC 和生物膜根除率在存在和不存在 AlgL 的情况下。还测量了氨基糖苷类与 DNase 和/或 AlgL 对抗囊性纤维化 (CF) 痰中内源性铜绿假单胞菌的协同活性。还检测了粘蛋白在粘液溶解剂NAC存在和不存在下对氨基糖苷活性的抑制作用。脂质体氨基糖苷类的MIC值与游离氨基糖苷类相似或更低。生物膜的形成使这些药物的杀菌浓度增加了 8 至 256 倍，并且用 AlgL 处理可提高对粘液菌株的杀灭作用。添加 DNase 或 AlgL 后，一些氨基糖苷类药物的抗痰活性会增加 (P < 0.05)，并且随着同时使用 DNase 和 AlgL，这种活性越来越明显。添加粘蛋白对脂质体氨基糖苷活性的抑制（高达32倍）明显多于游离氨基糖苷（高达8倍）。添加NAC并没有显着提高活性（P > 0.05）。妥布霉素是减少生物膜和痰液最有效的氨基糖苷类药物。脂质体氨基糖苷类药物的效果并不比传统形式更好。 DNase 和 AlgL 的共同给药对于增强减少生物膜生长和痰细菌计数的活性至关重要。虽然粘蛋白会延缓杀菌活性，但 NAC 不会提高氨基糖苷活性。
This study evaluated the potential of DNase, alginate lyase (AlgL) and N-acetylcysteine (NAC) in enhancing the in vitro bactericidal activity of conventional (free) and vesicle-entrapped (liposomal) gentamicin, amikacin and tobramycin.The MICs and biofilm eradication for two clinical isolates of Pseudomonas aeruginosa (a mucoid strain and a non-mucoid strain) were determined in the presence and absence of AlgL. The co-activity of aminoglycosides with DNase and/or AlgL against endogenous P. aeruginosa in cystic fibrosis (CF) sputum was also measured. The inhibitory effects of mucin in the presence and absence of the mucolytic agent NAC on aminoglycosidic activity were also examined.The MIC values of the liposomal aminoglycosides were similar to or lower than those of free aminoglycosides. Biofilm formation increased the bactericidal concentrations of these drugs by 8- to 256-fold and treatment with AlgL improved killing of the mucoid strain. The activity of some aminoglycosides against the sputum was increased by the addition of DNase or AlgL (P < 0.05), and was increasingly evident with concurrent DNase and AlgL administration. Addition of mucin inhibited liposomal aminoglycosidic activity (up to 32-fold) evidently more than the free aminoglycosides (up to 8-fold). The addition of NAC did not improve activity significantly (P > 0.05). Tobramycin was the most effective aminoglycoside to reduce biofilms and sputum.Liposomal aminoglycosides do not fare better than conventional forms. The co-administration of DNase and AlgL is essential for enhanced activity in reducing biofilm growth and sputum bacterial counts. While mucin retards bactericidal activity, NAC does not improve aminoglycosidic activity.