Department of Mechanical Engineering, University of California Merced, Merced, California, USA.
Department of Molecular and Cell Biology, University of California Merced, Merced, California, USA.
mSphere. 2020 Nov 4;5(6):e00946-20. doi: 10.1128/mSphere.00946-20.
is an opportunistic fungal pathogen of humans known for its ability to cause a wide range of infections. One major virulence factor of is its ability to form hyphae that can invade host tissues and cause disseminated infections. Here, we introduce a method based on atomic force microscopy to investigate hyphae on silicone elastomer substrates, focusing on the effects of temperature and antifungal drugs. Hyphal growth rates differ significantly for measurements performed at different physiologically relevant temperatures. Furthermore, it is found that fluconazole is more effective than caspofungin in suppressing hyphal growth. We also investigate the effects of antifungal drugs on the mechanical properties of hyphal cells. An increase in Young's modulus and a decrease in adhesion force are observed in hyphal cells subjected to caspofungin treatment. Young's moduli are not significantly affected following treatment with fluconazole; the adhesion force, however, increases. Overall, our results provide a direct means of observing the effects of environmental factors and antifungal drugs on hyphal growth and mechanics with high spatial resolution. is one of the most common pathogens of humans. One important virulence factor of is its ability to form elongated hyphae that can invade host tissues and cause disseminated infections. Here, we show the effect of different physiologically relevant temperatures and common antifungal drugs on the growth and mechanical properties of hyphae using atomic force microscopy. We demonstrate that minor temperature fluctuations within the normal range can have profound effects on hyphal cell growth and that different antifungal drugs impact hyphal cell stiffness and adhesion in different ways.
是一种机会性真菌病原体,能够引起广泛的感染。其主要毒力因子之一是能够形成菌丝,能够侵入宿主组织并引起播散性感染。在这里,我们介绍了一种基于原子力显微镜的方法来研究在硅橡胶弹性体基底上的菌丝,重点研究了温度和抗真菌药物的影响。在不同生理相关温度下进行的测量中,菌丝的生长速率有显著差异。此外,发现氟康唑比卡泊芬净更能抑制菌丝生长。我们还研究了抗真菌药物对菌丝细胞机械性能的影响。在卡泊芬净处理的菌丝细胞中观察到杨氏模量增加和粘附力降低。用氟康唑处理后,杨氏模量没有显著变化;然而,粘附力增加。总体而言,我们的结果提供了一种直接观察环境因素和抗真菌药物对菌丝生长和力学影响的方法,具有高空间分辨率。是人类最常见的病原体之一。的一个重要毒力因子是其形成细长菌丝的能力,这些菌丝能够侵入宿主组织并引起播散性感染。在这里,我们使用原子力显微镜显示了不同生理相关温度和常见抗真菌药物对菌丝生长和机械性能的影响。我们证明,正常范围内的微小温度波动会对菌丝细胞生长产生深远影响,并且不同的抗真菌药物以不同的方式影响菌丝细胞的刚性和粘附力。