Instituto de Agroquímica y Tecnología de los Alimentos, IATA-CSIC, Burjassot, Spain.
BMC Genomics. 2012 Aug 23;13:419. doi: 10.1186/1471-2164-13-419.
In recent years an increasing number of yeast infections in humans have been related to certain clinical isolates of Saccharomyces cerevisiae. Some clinical strains showed in vivo and in vitro virulence traits and were able to cause death in mice whereas other clinical strains were avirulent.
In this work, we studied the transcriptional profiles of two S. cerevisiae clinical strains showing virulent traits and two control non-virulent strains during a blood incubation model and detected a specific transcriptional response of clinical strains. This response involves an mRNA levels increase of amino acid biosynthesis genes and especially oxidative stress related genes. We observed that the clinical strains were more resistant to reactive oxygen species in vitro. In addition, blood survival of clinical isolates was high, reaching similar levels to pathogenic Candida albicans strain. Furthermore, a virulent strain mutant in the transcription factor Yap1p, unable to grow in oxidative stress conditions, presented decreased survival levels in human blood compared with the wild type or YAP1 reconstituted strain.
Our data suggest that this enhanced oxidative stress response in virulent clinical isolates, presumably induced in response to oxidative burst from host defense cells, is important to increase survival in human blood and can help to infect and even produce death in mice models.
近年来,越来越多的人类酵母菌感染与某些临床分离的酿酒酵母有关。一些临床菌株表现出体内和体外的毒力特征,并能够导致小鼠死亡,而其他临床菌株则没有毒力。
在这项工作中,我们研究了两个表现出毒力特征的酿酒酵母临床菌株和两个对照非毒力菌株在血液孵育模型中的转录谱,并检测到临床菌株的特定转录反应。该反应涉及氨基酸生物合成基因和特别是与氧化应激相关基因的 mRNA 水平增加。我们观察到临床菌株在体外对活性氧的抵抗能力更强。此外,临床分离株在血液中的存活能力较高,达到与致病性白念珠菌菌株相似的水平。此外,转录因子 Yap1p 突变的毒力菌株在氧化应激条件下无法生长,与野生型或 YAP1 重建菌株相比,其在人血中的存活水平降低。
我们的数据表明,这种增强的氧化应激反应在毒力临床分离株中很重要,可能是对宿主防御细胞的氧化爆发的反应,有助于增加在人血中的存活能力,并有助于感染甚至导致小鼠模型死亡。