O'May Che Y, Sanderson Kevin, Roddam Louise F, Kirov Sylvia M, Reid David W
Menzies Research Institute, University of Tasmania Clinical School, 43 Collins Street, Hobart, Tasmania 7001, Australia.
School of Medicine, University of Tasmania Clinical School, 43 Collins Street, Hobart, Tasmania 7001, Australia.
J Med Microbiol. 2009 Jun;58(Pt 6):765-773. doi: 10.1099/jmm.0.004416-0.
The success of Pseudomonas aeruginosa in cystic fibrosis (CF) and other chronic infections is largely attributed to its ability to grow in antibiotic-resistant biofilm communities. This study investigated the effects of limiting iron levels as a strategy for preventing/disrupting P. aeruginosa biofilms. A range of synthetic and naturally occurring iron-chelating agents were examined. Biofilm development by P. aeruginosa strain PAO1 and CF sputum isolates from chronically infected individuals was significantly decreased by iron removal under aerobic atmospheres. CF strains formed poor biofilms under anaerobic conditions. Strain PAO1 was also tested under anaerobic conditions. Biofilm formation by this model strain was almost totally prevented by several of the chelators tested. The ability of synthetic chelators to impair biofilm formation could be reversed by iron addition to cultures, providing evidence that these effective chelating compounds functioned by directly reducing availability of iron to P. aeruginosa. In contrast, the biological chelator lactoferrin demonstrated enhanced anti-biofilm effects as iron supplementation increased. Hence biofilm inhibition by lactoferrin appeared to occur through more complex mechanisms to those of the synthetic chelators. Overall, our results demonstrate the importance of iron availability to biofilms and that iron chelators have potential as adjunct therapies for preventing biofilm development, especially under low oxygen conditions such as encountered in the chronically infected CF lung.
铜绿假单胞菌在囊性纤维化（CF）及其他慢性感染中取得成功，很大程度上归因于其在抗生素耐药生物膜群落中生长的能力。本研究调查了限制铁水平作为预防/破坏铜绿假单胞菌生物膜策略的效果。研究了一系列合成及天然存在的铁螯合剂。在有氧环境下，通过去除铁，铜绿假单胞菌PAO1菌株及来自慢性感染个体的CF痰液分离株的生物膜形成显著减少。CF菌株在厌氧条件下形成的生物膜较差。PAO1菌株也在厌氧条件下进行了测试。几种测试的螯合剂几乎完全阻止了该模型菌株的生物膜形成。向培养物中添加铁可逆转合成螯合剂损害生物膜形成的能力，这证明这些有效的螯合化合物通过直接降低铜绿假单胞菌可利用的铁量发挥作用。相比之下，随着铁补充量增加，生物螯合剂乳铁蛋白表现出增强的抗生物膜作用。因此，乳铁蛋白对生物膜的抑制作用似乎通过比合成螯合剂更复杂的机制发生。总体而言，我们的结果证明了铁的可利用性对生物膜的重要性，并且铁螯合剂有潜力作为预防生物膜形成的辅助疗法，尤其是在慢性感染的CF肺部所遇到的低氧条件下。
