School of Life Sciences, Mayo Clinic Collaborative Research Building, Arizona State University, Scottsdale, AZ 85259, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ 85054, USA.
Glycobiology. 2020 Feb 19;30(3):186-197. doi: 10.1093/glycob/cwz092.
Coccidioides spp. are important pneumonia-causing pathogens of the American southwest, but little is known about their glycobiology and how their glycosylations differ from other pneumonia-causing fungi. There is mounting preliminary evidence to suggest genus or even species-specific glycosylations in the fungal kingdom due to the presence of unique carbohydrate-active enzymes (CAZymes) in fungal genomes (Deshpande et al. 2008, Glycobiology, 18(8), 626-637; Karkowska-Kuleta and Kozik 2015, Acta Biochim Pol., 62(3), 339-351). If Coccidioides spp.-specific glycans can be identified, it may be possible to exploit these differences to develop more specific diagnostic approaches and more effective therapeutics. Herein, we i) mined Coccidioides spp. and other pathogenic fungal genomes to identify CAZymes specific for Coccidioides spp., ii) proteomically determined the Coccidioides spp. "CAZome" produced in vivo and in vitro, and iii) utilized glycomics to differentiate Coccidioides genus-specific N-glycans from other pathogenic fungi. As far as we are aware, this is the first proteomic and glycomic comparison of the N-glycomes and CAZomes of different fungal genera during infection in human hosts.
球腔菌属是美国西南部重要的引起肺炎的病原体,但人们对其糖生物学知之甚少,也不知道其糖基化与其他引起肺炎的真菌有何不同。由于真菌基因组中存在独特的碳水化合物活性酶(CAZymes),初步证据表明真菌界存在属甚至种特异性的糖基化(Deshpande 等人,2008 年,《糖生物学》,18(8),626-637;Karkowska-Kuleta 和 Kozik,2015 年,《波兰生物化学学报》,62(3),339-351)。如果能鉴定出球腔菌属特有的聚糖,也许有可能利用这些差异开发更具特异性的诊断方法和更有效的疗法。在此,我们 i)挖掘球腔菌属和其他致病性真菌基因组,以鉴定针对球腔菌属的 CAZymes,ii)通过蛋白质组学确定体内和体外产生的球腔菌属“CAZome”,以及 iii)利用糖组学来区分球腔菌属特有的 N-聚糖与其他致病性真菌。据我们所知,这是首次在人类宿主感染过程中对不同真菌属的 N-聚糖组和 CAZome 进行蛋白质组学和糖组学比较。