Myers Ryan R, Smith Timothy D, Elsawa Sherine F, Puel Olivier, Tadrist Souraia, Calvo Ana M
Department of Biological Sciences, Northern Illinois University, Dekalb, Illinois, United States of America.
Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
PLoS One. 2017 Apr 28;12(4):e0176702. doi: 10.1371/journal.pone.0176702. eCollection 2017.
Invasive aspergillosis by Aspergillus fumigatus is a leading cause of infection-related mortality in immune-compromised patients. In order to discover potential genetic targets to control A. fumigatus infections we characterized rtfA, a gene encoding a putative RNA polymerase II transcription elongation factor-like protein. Our recent work has shown that the rtfA ortholog in the model fungus Aspergillus nidulans regulates morphogenesis and secondary metabolism. The present study on the opportunistic pathogen A. fumigatus rtfA gene revealed that this gene influences fungal growth and conidiation, as well as production of the secondary metabolites tryptoquivaline F, pseurotin A, fumiquinazoline C, festuclavine, and fumigaclavines A, B and C. Additionally, rtfA influences protease activity levels, the sensitivity to oxidative stress and adhesion capacity, all factors important in pathogenicity. Furthermore, rtfA was shown to be indispensable for normal virulence using Galleria mellonella as well as murine infection model systems.
烟曲霉引起的侵袭性曲霉病是免疫功能低下患者感染相关死亡的主要原因。为了发现控制烟曲霉感染的潜在基因靶点,我们对rtfA进行了表征,rtfA是一个编码假定的RNA聚合酶II转录延伸因子样蛋白的基因。我们最近的研究表明,模式真菌构巢曲霉中的rtfA直系同源基因调节形态发生和次级代谢。目前对机会性病原体烟曲霉rtfA基因的研究表明,该基因影响真菌生长和分生孢子形成,以及次级代谢产物色氨酸缬氨酸F、伪曲菌素A、烟曲喹唑啉C、麦角胺和烟曲霉环肽A、B和C的产生。此外,rtfA影响蛋白酶活性水平、对氧化应激的敏感性和黏附能力,这些都是致病性的重要因素。此外,使用大蜡螟以及小鼠感染模型系统表明,rtfA对于正常毒力是不可或缺的。