Da Wenyue, Shao Jing, Li Qianqian, Shi Gaoxiang, Wang Tianming, Wu Daqiang, Wang Changzhong
Department of Pathogenic Biology and Immunology, College of Integrated Chinese and Western Medicine (College of Life Science), Anhui University of Chinese Medicine, Hefei, China.
Front Microbiol. 2019 Jan 25;10:34. doi: 10.3389/fmicb.2019.00034. eCollection 2019.
is a commonly isolated opportunistic yeast and can endanger immune-compromised human health. As increasingly isolated strains present resistance to currently used antifungals, it is necessary to develop novel antimycotics. In a previous study, sodium houttuyfonate (SH) alone or in combination with fluconazole revealed relatively strong antifungal potential against , and the underlying mechanism might be likely to be associated with β-glucan synthesis and transportation (Shao et al., 2017). In the present experiment, we used a standard isolate and a phr1 mutant (-/-) to investigate the interaction of SH with β-glucan, one of the critical components in cell wall and biofilm matrix. We showed that lyticase was the most effective enzyme that could significantly increase the antifungal inhibition of SH at 64 μg/mL in SC5314 but became futile in -/-. Although the minimum inhibitory concentrations (MICs) of SH were comparable in the two strains used, -/- appeared to be more susceptible to SH compared with SC5314 in biofilms (64 versus 512 μg/mL). The peak areas of SH decreased markedly by 71.6, 38.2, and 62.6% in SC5314 and by 70% and 53.2% in -/- by ultra-performance liquid chromatography (UPLC) analysis after co-incubation of SH with laminarin, extracellular matrix (EM) and cell wall. The chitin appeared to not interact with SH. We further demonstrated that sub-MIC SH (8 μg/mL) was able to induce cell wall remodeling by unmasking β-1,3-glucan and chitin in both SC5314 and -/-. Based on these findings, we propose that β-1,3-glucan can block the entrance of SH through non-specific absorption, and then the fungus senses the interaction of SH with β-1,3-glucan and exposes more β-1,3-glucan that contributes to SH blocking in turn.
是一种常见的分离机会性酵母，可危及免疫功能低下人群的健康。由于越来越多的分离菌株对目前使用的抗真菌药物产生耐药性，因此有必要开发新型抗真菌药物。在先前的一项研究中，鱼腥草素钠（SH）单独或与氟康唑联合使用时，对 显示出相对较强的抗真菌潜力，其潜在机制可能与β-葡聚糖的合成和运输有关（Shao等人，2017年）。在本实验中，我们使用标准 分离株和phr1突变体（-/-）来研究SH与β-葡聚糖（细胞壁和生物膜基质中的关键成分之一）的相互作用。我们发现溶菌酶是最有效的酶，它可以显著增加SH在64μg/mL时对SC5314的抗真菌抑制作用，但在-/-中则无效。尽管SH在所用的两种 菌株中的最低抑菌浓度（MIC）相当，但与SC5314相比，-/-在生物膜中似乎对SH更敏感（64对512μg/mL）。在将SH与海带多糖、细胞外基质（EM）和细胞壁共同孵育后，通过超高效液相色谱（UPLC）分析，SC5314中SH的峰面积显著下降了71.6%、38.2%和62.6%，-/-中分别下降了70%和53.2%。几丁质似乎不与SH相互作用。我们进一步证明，亚MIC SH（8μg/mL）能够通过在SC5314和-/-中暴露β-1,3-葡聚糖和几丁质来诱导细胞壁重塑。基于这些发现，我们提出β-1,3-葡聚糖可以通过非特异性吸收阻止SH的进入，然后真菌感知SH与β-1,3-葡聚糖的相互作用，并暴露更多的β-1,3-葡聚糖，进而有助于SH的阻断。
