Ahmadi Mohammed S, Lee Hiu Ham, Sanchez David A, Friedman Adam J, Tar Moses T, Davies Kelvin P, Nosanchuk Joshua D, Martinez Luis R
Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA.
Howard University College of Medicine, Washington, DC, USA.
Antimicrob Agents Chemother. 2016 Mar 25;60(4):2185-94. doi: 10.1128/AAC.02659-15. Print 2016 Apr.
Candida albicansis a leading nosocomial pathogen. Today, candidal biofilms are a significant cause of catheter infections, and such infections are becoming increasingly responsible for the failure of medical-implanted devices.C. albicansforms biofilms in which fungal cells are encased in an autoproduced extracellular polysaccharide matrix. Consequently, the enclosed fungi are protected from antimicrobial agents and host cells, providing a unique niche conducive to robust microbial growth and a harbor for recurring infections. Here we demonstrate that a recently developed platform comprised of nanoparticles that release therapeutic levels of nitric oxide (NO-np) inhibits candidal biofilm formation, destroys the extracellular polysaccharide matrices of mature fungal biofilms, and hinders biofilm development on surface biomaterials such as the lumen of catheters. We found NO-np to decrease both the metabolic activity of biofilms and the cell viability ofC. albicansin vitroandin vivo Furthermore, flow cytometric analysis found NO-np to induce apoptosis in biofilm yeast cellsin vitro Moreover, NO-np behave synergistically when used in combination with established antifungal drug therapies. Here we propose NO-np as a novel treatment modality, especially in combination with standard antifungals, for the prevention and/or remediation of fungal biofilms on central venous catheters and other medical devices.
白色念珠菌是一种主要的医院病原体。如今,念珠菌生物膜是导管感染的重要原因,而且此类感染对医用植入设备的失效责任越来越大。白色念珠菌形成生物膜,其中真菌细胞被包裹在自身产生的细胞外多糖基质中。因此,被包裹的真菌受到抗菌剂和宿主细胞的保护,提供了一个有利于强大微生物生长的独特生态位以及反复感染的庇护所。在这里,我们证明了一个最近开发的由释放治疗水平一氧化氮的纳米颗粒组成的平台(NO-np)可抑制念珠菌生物膜的形成,破坏成熟真菌生物膜的细胞外多糖基质,并阻碍生物膜在诸如导管内腔等表面生物材料上的形成。我们发现NO-np在体外和体内均可降低生物膜的代谢活性以及白色念珠菌的细胞活力。此外,流式细胞术分析发现NO-np在体外可诱导生物膜酵母细胞凋亡。此外,NO-np与既定的抗真菌药物疗法联合使用时具有协同作用。在这里,我们提出NO-np作为一种新型治疗方式,特别是与标准抗真菌药物联合使用时,用于预防和/或修复中心静脉导管和其他医疗设备上的真菌生物膜。