California Institute for Medical Research, San Jose, California, United States of America.
Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
PLoS One. 2019 May 8;14(5):e0216085. doi: 10.1371/journal.pone.0216085. eCollection 2019.
Pseudomonas aeruginosa and Aspergillus fumigatus are pathogens frequently co-inhabiting immunocompromised patient airways, particularly in people with cystic fibrosis. Both microbes depend on the availability of iron, and compete for iron in their microenvironment. We showed previously that the P. aeruginosa siderophore pyoverdine is the main instrument in battling A. fumigatus biofilms, by iron chelation and denial of iron to the fungus. Here we show that A. fumigatus siderophores defend against anti-fungal P. aeruginosa effects. P. aeruginosa supernatants produced in the presence of wildtype A. fumigatus planktonic supernatants (Afsup) showed less activity against A. fumigatus biofilms than P. aeruginosa supernatants without Afsup, despite higher production of pyoverdine by P. aeruginosa. Supernatants of A. fumigatus cultures lacking the sidA gene (AfΔsidA), unable to produce hydroxamate siderophores, were less capable of protecting A. fumigatus biofilms from P. aeruginosa supernatants and pyoverdine. AfΔsidA biofilm was more sensitive towards inhibitory effects of pyoverdine, the iron chelator deferiprone (DFP), or amphothericin B than wildtype A. fumigatus biofilm. Supplementation of sidA-deficient A. fumigatus biofilm with A. fumigatus siderophores restored resistance to pyoverdine. The A. fumigatus siderophore production inhibitor celastrol sensitized wildtype A. fumigatus biofilms towards the anti-fungal activity of DFP. In conclusion, A. fumigatus hydroxamate siderophores play a pivotal role in A. fumigatus competition for iron against P. aeruginosa.
铜绿假单胞菌和烟曲霉是经常共同寄居在免疫功能低下患者气道中的病原体，尤其在囊性纤维化患者中更为常见。这两种微生物都依赖铁的可用性，并在其微环境中争夺铁。我们之前曾表明，铜绿假单胞菌的铁载体绿脓菌素是对抗烟曲霉生物膜的主要手段，通过螯合铁和剥夺真菌铁。在这里，我们表明烟曲霉的铁载体可以抵御抗真菌铜绿假单胞菌的作用。在存在野生型烟曲霉浮游生物上清液（Afsup）的情况下产生的铜绿假单胞菌上清液比没有 Afsup 的铜绿假单胞菌上清液对烟曲霉生物膜的活性更低，尽管铜绿假单胞菌产生的绿脓菌素更多。缺乏 sidA 基因（AfΔsidA）的烟曲霉培养物的上清液不能产生羟肟酸类铁载体，因此更不能保护烟曲霉生物膜免受铜绿假单胞菌上清液和绿脓菌素的影响。AfΔsidA 生物膜比野生型烟曲霉生物膜对绿脓菌素、铁螯合剂地拉罗司（DFP）或两性霉素 B 的抑制作用更为敏感。用烟曲霉铁载体补充 sidA 缺陷型烟曲霉生物膜可以恢复对绿脓菌素的抗性。烟曲霉铁载体产生抑制剂 celastrol 使野生型烟曲霉生物膜对 DFP 的抗真菌活性变得敏感。总之，烟曲霉的羟肟酸类铁载体在烟曲霉与铜绿假单胞菌争夺铁的竞争中起着关键作用。
