Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America.
PLoS Pathog. 2010 Mar 26;6(3):e1000827. doi: 10.1371/journal.ppat.1000827.
Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection.
在免疫功能正常的宿主中,白色念珠菌是人类微生物群中的良性成员。然而,当宿主生理功能被打乱时,这种共生-宿主相互作用可能会恶化,并导致机会性感染。关于白色念珠菌定植和发病机制的动态变化,我们知之甚少。我们开发了一种白色念珠菌细胞表面蛋白微阵列,以分析共生定植和念珠菌血症期间的免疫球蛋白 G 反应。来自念珠菌血症患者和我们的阴性对照组的血清抗体反应表明,免疫功能正常的宿主与共生白色念珠菌之间存在着永久性的宿主-病原体相互作用。本报告还确定了与念珠菌血症不同阶段(即急性、早期和中期恢复期)相关的细胞表面抗原。我们确定了一组 13 种细胞表面抗原,能够将急性念珠菌血症与健康个体和携带共生菌定植的未感染医院患者区分开来。有趣的是,这些细胞表面抗原中有很大一部分参与了氧化应激或耐药性。此外,我们还鉴定出在念珠菌血症患者恢复期血清中富集的 33 种抗原性蛋白。有趣的是,我们在这个亚组中发现了与血红素相关铁摄取相关的抗原增加。这些发现对白色念珠菌定植的机制以及系统性感染的发展具有重要意义。