Mahdiun Faeze, Mansouri Shahla, Khazaeli Payam, Mirzaei Rasoul
Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Department of Microbiology and Virology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Microb Pathog. 2017 Jun;107:129-135. doi: 10.1016/j.micpath.2017.03.014. Epub 2017 Mar 18.
Pseudomonas aeruginosa is an opportunistic pathogen, enable of causing infections especially in immunocompromised patients. Recently many isolates developed multiple drug resistance, resulting in treatment failure in serious infections. In this study, the effect of tobramycin incorporated with bismuth-ethanedithiol loaded on niosomes on the quorum sensing and biofilm production by P. aeruginosa was evaluated. Thin layer hydration method with cholesterol (30%), Span 40 and Tween 40 were used to make niosomes. The physical properties and particle size of the niosomes were investigated. Micro dilution method was used to determine the Minimum Inhibitory Concentration (MIC) for tobramycin, niosomal tobramycin, bismuth ethanedithiol, niosomal bismuth ethanedithiol, tobramycin incorporated with bismuth-ethanedithiol and niosomal tobramycin incorporated with bismuth-ethanedithiol. Biofilm formation was evaluated using microtiter plate. The effect of different combination on N-acyl homoserine lactone (AHL) production was evaluated in presence of Agrobacterium tumefaciens strain (GV3101). The best combination inhibiting the growth of various strains of P. aeruginosa were niosomal tobramycin and niosomal tobramycin incorporated with bismuth-ethanedithiol which reduced the MIC of tobramycin significantly. Sub-MIC concentration of these compounds reduced the rate of biofilm formation 80% lower than the untreated bacteria, and effectively inhibited the production of AHL molecule. The prepared formulations containing non-ionic surfactants, can kept the drug and gradually release it. Encapsulation of tobramycin in combination with bismuth-ethanedithiol in niosome had the ability to reduce the MIC of tobramycin and effectively inhibiting the biofilm formation. These combinations can be used as an excellent combination for further evaluation for treatment of infections caused by MDR isolates of P. aeruginosa.
铜绿假单胞菌是一种机会致病菌，尤其能够在免疫功能低下的患者中引起感染。最近，许多分离株产生了多重耐药性，导致严重感染的治疗失败。在本研究中，评估了负载于脂质体上的妥布霉素与乙二硫醇铋结合对铜绿假单胞菌群体感应和生物膜形成的影响。采用胆固醇（30%）、司盘40和吐温40的薄膜水化法制备脂质体。研究了脂质体的物理性质和粒径。采用微量稀释法测定妥布霉素、脂质体妥布霉素、乙二硫醇铋、脂质体乙二硫醇铋、妥布霉素与乙二硫醇铋结合物以及脂质体妥布霉素与乙二硫醇铋结合物的最低抑菌浓度（MIC）。使用微量滴定板评估生物膜形成。在根癌农杆菌菌株（GV3101）存在的情况下，评估不同组合对N-酰基高丝氨酸内酯（AHL）产生的影响。抑制各种铜绿假单胞菌菌株生长的最佳组合是脂质体妥布霉素和脂质体妥布霉素与乙二硫醇铋结合物，它们显著降低了妥布霉素的MIC。这些化合物的亚MIC浓度使生物膜形成率比未处理的细菌降低了80%，并有效抑制了AHL分子的产生。所制备的含有非离子表面活性剂的制剂能够保持药物并使其逐渐释放。将妥布霉素与乙二硫醇铋结合封装在脂质体中能够降低妥布霉素的MIC并有效抑制生物膜形成。这些组合可作为一种优秀的组合，用于进一步评估治疗由多重耐药铜绿假单胞菌分离株引起的感染。
