Dept. of Biomedical Sciences, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Int J Med Microbiol. 2011 Aug;301(6):536-46. doi: 10.1016/j.ijmm.2010.12.002. Epub 2011 Mar 2.
Systemic infections of Candida albicans, the most prevalent fungal pathogen in humans, are on the rise in recent years. However, the exact mode of pathogenesis of this fungus is still not well elucidated. Previous studies using C. albicans mutants locked into the yeast form via gene deletion found that this form was avirulent and did not induce significant differential expression of host genes in vitro. In this study, a high density of C. albicans was used to infect human umbilical vein endothelial cells (HUVEC), resulting in yeast-form infections, whilst a low density of C. albicans resulted in hyphae infections. Transcriptional profiling of HUVEC response to these infections showed that high densities of C. albicans induced a stronger, broader transcriptional response from HUVEC than low densities of C. albicans infection. Many of the genes that were significantly differentially expressed were involved in apoptosis and cell death. In addition, conditioned media from the high-density infections caused a significant reduction in HUVEC viability, suggesting that certain molecules released during C. albicans and HUVEC interactions were capable of causing cell death. This study has shown that C. albicans yeast-forms, at high densities, cannot be dismissed as avirulent, but instead could possibly contribute to C. albicans pathogenesis.
近年来，人类最常见的真菌病原体白念珠菌的系统性感染呈上升趋势。然而，这种真菌的确切发病机制仍未得到很好的阐明。先前使用通过基因缺失锁定在酵母形式的白念珠菌突变体的研究发现，这种形式没有毒力，不会在体外诱导宿主基因的显著差异表达。在这项研究中，高浓度的白念珠菌感染人脐静脉内皮细胞（HUVEC），导致酵母形式的感染，而低浓度的白念珠菌感染导致菌丝形式的感染。对白念珠菌感染 HUVEC 后 HUVEC 反应的转录谱分析表明，与低浓度的白念珠菌感染相比，高浓度的白念珠菌诱导了 HUVEC 更强、更广泛的转录反应。许多显著差异表达的基因参与细胞凋亡和死亡。此外，高浓度感染的条件培养基导致 HUVEC 活力显著降低，这表明在白念珠菌和 HUVEC 相互作用过程中释放的某些分子能够导致细胞死亡。这项研究表明，高浓度的白念珠菌酵母形式不能被视为无毒，反而可能有助于白念珠菌的发病机制。
