Abstract

Airways of immunocompromised patients, or individuals with cystic fibrosis (CF), are common ground for Pseudomonas aeruginosa and Aspergillus fumigatus infections. Hence, in such a microenvironment both pathogens compete for resources. While under limiting iron conditions the siderophore pyoverdine is the most effective antifungal P. aeruginosa product, we now provide evidence that under nonlimiting iron conditions P. aeruginosa supernatants lack pyoverdine but still possess considerable antifungal activity. Spectrometric analyses of P. aeruginosa supernatants revealed the presence of phenazines, such as pyocyanin, only under nonlimiting iron conditions. Supernatants of quorum sensing mutants of strain PA14, defective in phenazine production, as well as supernatants of the P. aeruginosa strain PAO1, lacked pyocyanin, and were less inhibitory toward A. fumigatus biofilms under nonlimiting iron conditions. When blood as a natural source of iron was present during P. aeruginosa supernatant production, pyoverdine was absent, and phenazines, including pyocyanin, appeared, resulting in an antifungal effect on A. fumigatus biofilms. Pure pyocyanin reduced A. fumigatus biofilm metabolism. In summary, P. aeruginosa has mechanisms to compete with A. fumigatus under limiting and non-limiting iron conditions, and can switch from iron-denial-based to toxin-based antifungal activity. This has implications for the evolution of the microbiome in clinical settings where the two pathogens co-exist. Important differences in the iron response of P. aeruginosa laboratory strains PA14 and PAO1 were also uncovered.

中文翻译：

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在非限制性铁条件下，绿脓素是一种主要的抗真菌分子，并且原型铜绿假单胞菌菌株之间存在差异

摘要

免疫功能低下患者或囊性纤维化 (CF) 患者的气道是铜绿假单胞菌和烟曲霉感染的共同基础。因此，在这样的微环境中，两种病原体都在争夺资源。虽然在限制铁条件下，铁载体 pyoverdine 是最有效的抗真菌铜绿假单胞菌产品，但我们现在提供的证据表明，在非限制铁条件下，铜绿假单胞菌上清液缺乏 pyoverdine，但仍具有相当大的抗真菌活性。铜绿假单胞菌的光谱分析上清液仅在非限制性铁条件下才显示吩嗪（如绿脓素）的存在。PA14 菌株群体感应突变体的上清液，吩嗪生产有缺陷，以及铜绿假单胞菌PAO1 菌株的上清液缺乏绿脓素，并且在非限制性铁条件下对烟曲霉生物膜的抑制作用较小。当在铜绿假单胞菌上清液生产过程中存在作为铁的天然来源的血液时，不存在铜绿素，并且出现吩嗪，包括绿脓素，从而对烟曲霉生物膜产生抗真菌作用。纯绿脓素降低了烟曲霉生物膜代谢。总之，铜绿假单胞菌具有在限制性和非限制性铁条件下与A. fumigatus竞争的机制，并且可以从基于铁的抗真菌活性转变为基于毒素的抗真菌活性。这对两种病原体共存的临床环境中微生物组的进化具有影响。还发现了铜绿假单胞菌实验室菌株 PA14 和 PAO1铁反应的重要差异。