Departments of Pediatrics, Texas Children's Hospital & Baylor College of Medicine, Houston, Texas 77030, USA.
Pediatr Res. 2011 Dec;70(6):578-83. doi: 10.1203/PDR.0b013e318232a984.
Biofilm infections are frequently caused by Staphylococcus epidermidis, are resistant to antimicrobial agents, and adversely affect patient outcomes. We evaluated farnesol (FSL), the Candida quorum-sensing molecule, on S. epidermidis biofilms, in vitro and in vivo. We evaluated ED50, ED75, and ED90 (drug concentrations causing 50%, 75%, and 90% inhibition, respectively) of FSL and evaluated synergy with nafcillin and vancomycin. FSL's effects on morphology of S. epidermidis biofilms were analyzed using confocal microscopy and real-time changes using a bioluminescent strain of S. epidermidis, Xen 43. In mice, effects of FSL treatment on s.c. catheter biofilms; cultures of blood, kidney, and catheter and pericatheter tissues; and bioluminescence in strain Xen 43 were evaluated. FSL inhibited biofilms (ED50 ranged from 0.625 to 2.5 mM) and was synergistic with nafcillin and vancomycin at most combination ratios. FSL significantly decreased biovolume, substratum coverage, and mean thickness of S. epidermidis biofilms. In mice, FSL significantly decreased viable colony counts of S. epidermidis from blood, kidney, and catheter and pericatheter tissues and decreased Xen 43 bioluminescence. We confirmed the antibiofilm effects of FSL both in vitro and in vivo, in a bioluminescent strain and its synergy with antibiotics. FSL may be effective against clinical S. epidermidis biofilm infections.
生物膜感染通常由表皮葡萄球菌引起,对抗菌药物有耐药性,并对患者的预后产生不良影响。我们评估了法尼醇(FSL),一种念珠菌群体感应分子,对表皮葡萄球菌生物膜的体外和体内作用。我们评估了 FSL 的 ED50、ED75 和 ED90(分别导致 50%、75%和 90%抑制的药物浓度),并评估了与萘夫西林和万古霉素的协同作用。使用共聚焦显微镜分析 FSL 对表皮葡萄球菌生物膜形态的影响,并使用表皮葡萄球菌生物发光株 Xen 43 实时分析变化。在小鼠中,评估 FSL 处理对皮下导管生物膜、血液、肾脏和导管及导管周围组织的培养物以及 Xen 43 菌株生物发光的影响。FSL 抑制生物膜(ED50 范围为 0.625 至 2.5 mM),并与萘夫西林和万古霉素在大多数组合比例下具有协同作用。FSL 显著降低了表皮葡萄球菌生物膜的生物量、基质覆盖率和平均厚度。在小鼠中,FSL 显著降低了血液、肾脏和导管及导管周围组织中表皮葡萄球菌的活菌计数,并降低了 Xen 43 的生物发光。我们在生物发光株及其与抗生素的协同作用中,在体外和体内证实了 FSL 的抗生物膜作用。FSL 可能对临床表皮葡萄球菌生物膜感染有效。