Iraqui Ismail, Garcia-Sanchez Susana, Aubert Sylvie, Dromer Françoise, Ghigo Jean-Marc, d'Enfert Christophe, Janbon Guilhem
Unité de Mycologie Moléculaire, INRA USC 2019, Paris, France.
Mol Microbiol. 2005 Feb;55(4):1259-71. doi: 10.1111/j.1365-2958.2004.04475.x.
Biofilm is the predominant type of microbial development in natural environments, and potentially represents a major form of resistance or source of recurrence during host infection. Although a large number of studies have focussed on the genetics of bacterial biofilm formation, very little is known about the genes involved in this type of growth in fungi. A genetic screen for Candida glabrata Biofilm mutants was performed using a 96-well plate model of biofilm formation. Study of the isolated mutant strains allowed the identification of four genes involved in biofilm formation (RIF1, SIR4, EPA6 and YAK1). Epa6p is a newly identified adhesin required for biofilm formation in this pathogenic yeast. EPA6 and its close paralogue EPA7 are located in subtelomeric regions and their transcription is regulated by Sir4p and Rif1p, two proteins involved in subtelomeric silencing. Biofilm growth conditions induce the transcription of EPA6 and EPA7: this is dependent on the presence of an intact subtelomeric silencing machinery and is independent of the Mpk1p signalling pathway. Finally, the kinase Yak1p is required for expression of both adhesin genes and acts through a subtelomeric silencing machinery-dependent pathway.
生物膜是自然环境中微生物生长的主要形式,在宿主感染期间可能是耐药的主要形式或复发的来源。尽管大量研究聚焦于细菌生物膜形成的遗传学,但对于参与真菌这种生长类型的基因却知之甚少。利用生物膜形成的96孔板模型对光滑念珠菌生物膜突变体进行了遗传筛选。对分离出的突变菌株的研究鉴定出了四个参与生物膜形成的基因(RIF1、SIR4、EPA6和YAK1)。Epa6p是这种致病酵母生物膜形成所需的一种新鉴定的粘附素。EPA6及其紧密同源物EPA7位于亚端粒区域,其转录受Sir4p和Rif1p调控,这两种蛋白质参与亚端粒沉默。生物膜生长条件可诱导EPA6和EPA7的转录:这依赖于完整的亚端粒沉默机制的存在,且独立于Mpk1p信号通路。最后,激酶Yak1p是两种粘附素基因表达所必需的,并通过依赖于亚端粒沉默机制的途径发挥作用。