Role of iron in biofilm formation

这项研究的目的是研究铁在生物膜形成中的作用。生物膜可在有生命或无生命的表面形成，并可普遍存在于自然、工业和医院环境中。微生物在许多不同因素的作用下形成生物膜，这些因素可能包括对表面附着位置的识别，和/或营养线索(例如细胞铁源)。铁是细菌生长所必需的。从NSERC以前资助的研究中，我们有证据表明，由我们的工业合作伙伴螯合伙伴公司(CPI)开发的新型铁络合剂Dibi能够与铁结合得比任何其他可用的铁络合剂强得多，使细菌细胞无法获得铁。因此，似乎有可能通过铁络合来抑制细菌生物膜的形成。我们将通过将细菌(铜绿假单胞菌)注入小鼠肺内，在体外细菌细胞培养和体内生物膜形成模型中研究铁在生物膜形成中的作用。我们将使用细菌学方法和肺部细菌生长的活体成像方法，将CPI生产的新型铁络合剂DIBI与已经商业化的铁络合剂(去铁胺-DFO、去铁酮-DFP、去铁-DFX)进行比较。我们还将分析注射不同铁络合剂后的组织和血浆样本。

The aim of the proposed research is to study the role of iron in biofilm formation. Biofilms may form on living or non-living surfaces and can be prevalent in natural, industrial, and hospital settings. Microbes form a biofilm in response to a number of different factors, which may include recognition of an attachment site on a surface, and/or nutritional cues (e.g. cellular iron sources). Iron is essential for bacterial growth. From previous NSERC-funded research we have evidence that the novel iron chelator, DIBI, by our industrial partner, Chelation Partners Inc. (CPI) is capable to bind iron much stronger than any other available iron chelator and makes it unavailable for bacterial cells. Therefore, it seems possible to suppress bacterial biofilm formation by iron chelation. We will study the role of iron in biofilm formation in bacterial cell cultures in vitro and in a model of biofilm formation in vivo by administering bacteria (Pseudomonas aeruginosa) to lungs of mice. We will compare the novel iron chelator, DIBI, from CPI with already commercialized iron chelators (deferoxamine - DFO, deferiprone - DFP, deferasirox - DFX) using bacteriological methods and intravital imaging of bacterial growth in the lungs. We will also analyze tissue and plasma samples following administration of different iron chelators.