School of Dentistry, Level 7, UQ Oral Health Centre, University of Queensland, Herston Road, Brisbane, QLD, 4006, Australia,
Mycopathologia. 2015 Apr;179(3-4):195-204. doi: 10.1007/s11046-014-9848-z. Epub 2014 Dec 17.
Candida albicans is a major agent of fungaemias and frequently causes systemic disease through seeded, blood stream dissemination. These infections, particularly common in hospitalized patients with central venous catheters (CVCs), appear to persevere due to biofilm reservoirs of the yeast that tend to develop on the device. Although it is known that candidal biofilms are intrinsically resistant to antifungals compared with their planktonic counterparts, there is a paucity of data on the expression of antifungal drug resistance genes (DRGs) in candidal biofilms in CVC reservoirs. Furthermore, notwithstanding the fact that CVCs are constantly bathed in human serum, there are no studies on the effect of the latter on the DRG expression in candidal biofilms. Hence, we developed in vitro biofilms of three different C. albicans strains on silicone CVC discs immersed in human serum and evaluated the temporal expression of nine antifungal DRGs. In an attempt to evaluate the effect of hyphal elements on DRG expression, we incorporated a hyphal mutant (HM) and its wild-type (WT) counterpart, as well as a fresh clinical isolate in the studies. Human serum significantly up-regulated DRG transcripts in Candida biofilms on CVCs, at different stages of biofilm growth, while the WT strain over-expressed more DRGs than the HM strain. Here, we report, for the first time, that both human serum and the hyphal elements of the yeast have a profound modulatory effect on DRG expression in C. albicans biofilms on CVCs.
白色念珠菌是真菌血症的主要病原体,通过播种、血流传播经常引起全身性疾病。这些感染,特别是在有中央静脉导管(CVC)的住院患者中很常见,似乎由于酵母的生物膜储层在装置上倾向于发展而持续存在。虽然已知与浮游生物相比,酵母生物膜对抗真菌药物具有内在的抗性,但关于 CVC 储层中酵母生物膜中抗真菌药物耐药基因(DRG)的表达的数据很少。此外,尽管 CVC 不断浸泡在人血清中,但没有研究后者对酵母生物膜中 DRG 表达的影响。因此,我们在浸入人血清的硅酮 CVC 盘上培养了三种不同的白色念珠菌菌株的体外生物膜,并评估了九个抗真菌 DRG 的时间表达。为了评估菌丝元素对抗真菌药物耐药基因表达的影响,我们在研究中加入了一个菌丝突变体(HM)及其野生型(WT)对照以及一个新的临床分离株。人血清在不同生物膜生长阶段显着上调了 CVC 上念珠菌生物膜中的 DRG 转录物,而 WT 菌株比 HM 菌株表达更多的 DRG。在这里,我们首次报道,人血清和酵母的菌丝元素对 CVC 上白色念珠菌生物膜中 DRG 表达有深远的调节作用。