Musk D J, Hergenrother P J
Department of Chemistry, Center of Advanced Materials for the Purification of Water with Systems, Roger Adams Lab, University of Illinois, Urbana, IL 61801, USA.
J Appl Microbiol. 2008 Aug;105(2):380-8. doi: 10.1111/j.1365-2672.2008.03751.x. Epub 2008 Feb 18.
To determine whether chelated sources of ferric iron were efficient inhibitors of biofilm formation in Pseudomonas aeruginosa and might be suitable for drug delivery to the lungs of cystic fibrosis (CF) patients via nebulization.
The response of P. aeruginosa biofilms to elevated iron concentrations in the form of eight structurally varied iron chelators in a microtitre plate assay for biofilm production was examined in the lab. Among these iron chelates, picolinic acid and acetohydroxamic acid-chelated iron were able to effectively thwart biofilm production in P. aeruginosa PA14 and in 20 clinical isolates of P. aeruginosa from a local hospital. The chelated iron sources showed excellent distribution in an Anderson cascade impactor model of particle size distribution in the human lung.
Ferric picolinate and ferric acetohydroxamate are effective anti-biofilm compounds against both lab and clinical strains of P. aeruginosa and are readily nebulized into particles of suitable size for lung delivery.
The data herein serve both to solidify the growing base of literature correlating high iron levels with biofilm inhibition in P. aeruginosa and to highlight the potential of these chelators as nebulized agents to combat biofilms of P. aeruginosa in CF patients.
确定三价铁的螯合来源是否为铜绿假单胞菌生物膜形成的有效抑制剂，以及是否适合通过雾化给药至囊性纤维化（CF）患者的肺部。
在实验室中，通过微量滴定板生物膜生成试验，检测了铜绿假单胞菌生物膜对八种结构各异的铁螯合剂形式的高铁浓度的反应。在这些铁螯合物中，吡啶甲酸和乙酰氧肟酸螯合铁能够有效阻止铜绿假单胞菌PA14以及当地医院分离出的20株铜绿假单胞菌临床菌株形成生物膜。在人肺颗粒大小分布的安德森级联撞击器模型中，螯合铁源显示出良好的分布。
吡啶甲酸铁和乙酰氧肟酸铁是针对铜绿假单胞菌实验室菌株和临床菌株的有效抗生物膜化合物，并且易于雾化成适合肺部给药的大小颗粒。
本文数据既有助于巩固将高铁水平与铜绿假单胞菌生物膜抑制相关联的文献基础，也突出了这些螯合剂作为雾化剂对抗CF患者铜绿假单胞菌生物膜的潜力。
