Role of iron in biofilm formation

本研究的目的是研究铁在生物膜形成中的作用。生物膜可在生物或非生物表面形成，并可在自然、工业和医院环境中普遍存在。微生物在对许多不同因素的响应中形成生物膜，这些因素可能包括对表面附着位点的识别和/或营养线索（例如细胞铁源）。铁是细菌生长所必需的。从以前nserc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）开发的新型铁螯合剂DIBI比任何其他可用的铁螯合剂都能更强地结合铁，使其无法用于细菌细胞。因此，铁螯合似乎有可能抑制细菌生物膜的形成。我们将研究铁在体外细菌细胞培养中形成生物膜的作用，并通过向小鼠肺中施用细菌（铜绿假单胞菌）来建立体内生物膜形成模型。我们将使用细菌学方法和肺部细菌生长的活体成像来比较CPI的新型铁螯合剂DIBI与已经商业化的铁螯合剂（去铁胺- DFO，去铁素- DFP，去铁素- DFX）。我们也将分析组织和血浆样本后，不同的铁螯合剂的管理。

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.