Host-yeast interactions are fundamental drivers of human microbiome dynamics,spanning a spectrum from mutualistic symbiosis to opportunistic pathogenesis with profound implications for systemic health.This review syst...Host-yeast interactions are fundamental drivers of human microbiome dynamics,spanning a spectrum from mutualistic symbiosis to opportunistic pathogenesis with profound implications for systemic health.This review systematically elucidates the complex molecular mechanisms governing these relationships,with a specific focus on metabolic interdependence and immunomodulation.We analyze how yeast-derived metabolites,particularly short-chain fatty acids(SCFAs),modulate host glucose and lipid homeostasis via signaling pathways such as GPR41/43 and GLP-1 secretion.Furthermore,the review explores the pathophysiological role of fungal dysbiosis in chronic conditions,including obesity,diabetes,and inflammatory bowel disease(IBD),highlighting how a breakdown in host-yeast homeostasis triggers pro-inflammatory cascades.Beyond the fungal-host axis,we introduce the concept of the"mycobiome-virome-bacterial axis,"discussing how commensal yeasts synergize with beneficial bacteria like Bifidobacterium and influence viral infectivity through Interferon-mediated innate immune priming.We critically evaluate how cutting-edge technologies-including transgenic mouse models(specifically Dectin-1^(-/-)and CARD9^(-/-),metabolomics,and single-cell sequencing-have revolutionized our mechanistic understanding of these multi-kingdom dynamics.By integrating current findings,we identify critical knowledge gaps and propose high-resolution research frameworks,such as humanized organ-on-a-chip systems,to simulate intricate host-microbe interactions under physiological flow conditions.This comprehensive synthesis provides a strategic foundation for developing targeted,next-generation microbiome-based interventions to restore host-yeast balance and enhance overall human health.展开更多
目的探讨氟康唑对阿萨希毛孢子菌(T.asahii)蛋白质组学的影响,从蛋白层面揭示T.asahii对氟康唑胁迫的响应过程及唑类耐药机制。方法以T.asahii AS 2.2174作为研究菌株,基于微量液基稀释法测定氟康唑的最低抑菌浓度(MIC)。应用串联质谱标...目的探讨氟康唑对阿萨希毛孢子菌(T.asahii)蛋白质组学的影响,从蛋白层面揭示T.asahii对氟康唑胁迫的响应过程及唑类耐药机制。方法以T.asahii AS 2.2174作为研究菌株,基于微量液基稀释法测定氟康唑的最低抑菌浓度(MIC)。应用串联质谱标签(TMT)技术结合液相色谱与串联质谱(LC-MS/MS)技术检测氟康唑(1×MIC)处理前后T.asahii蛋白丰度的变化。以差异倍数≥1.20或≤0.83,且P<0.05作为筛选标准,鉴定差异表达蛋白(DEPs)。对DEPs进行Gene Ontlogy(GO)和京都基因与基因组百科全书(KEGG)富集分析,以了解DEPs的生物学属性以及DEPs参与的主要生物学通路。最后,使用多反应监测(MRM)技术对目标差异蛋白进行靶向验证。结果氟康唑对T.asahii AS 2.2174的MIC值为8μg/ml。共鉴定到DEPs 196个,其中上调DEPs 93个,下调DEPs 103个。功能富集分析提示DEPs主要参与甾醇合成与代谢、药物代谢、应激反应、能量代谢及翻译等生物学过程。目标差异蛋白在MRM靶向验证和TMT-LC-MS/MS检测中具有一致的表达趋势。结论在氟康唑胁迫下,T.asahii蛋白丰度发生显著改变。生物信息学分析揭示了T.asahii响应氟康唑胁迫的复杂分子机制,这些机制对于了解T.asahii唑类耐药性及挖掘新的药物靶点提供了重要见解。展开更多
目的真菌的细胞膜上普遍存在高渗透压信号蛋白1(high osmolarity signaling protein 1,Sho1),其结构相对保守,在致病机制中发挥重要作用。然而,Sho1蛋白对白念珠菌致病能力的影响尚未见报道。因此,建立构建白念珠菌SHO1基因敲除株的方法...目的真菌的细胞膜上普遍存在高渗透压信号蛋白1(high osmolarity signaling protein 1,Sho1),其结构相对保守,在致病机制中发挥重要作用。然而,Sho1蛋白对白念珠菌致病能力的影响尚未见报道。因此,建立构建白念珠菌SHO1基因敲除株的方法,为后续深入探索Sho1蛋白对白念珠菌生物学性状及致病能力的影响提供了理论基础。方法基因敲除技术选择采用SN152(His-/Leu-/Arg-)缺陷株为亲本株,运用融合PCR技术和同源互补的His和Leu质粒,目的基因可以被快速有效地敲除。通过结晶紫染色实验观察生物膜形成能力、聚苯乙烯孔板模型检测其黏附能力、革兰染色油镜观察菌丝形态,初步探索了Sho1蛋白对白念珠菌致病能力的影响。结果构建了his和融合PCR-his基因敲除盒,leu和融合PCR-leu基因敲除盒并将它们电转化到SN152中,用缺陷培养基筛选敲除株。通过PCR、琼脂糖凝胶电泳和基因测序方法验证SHO1基因敲除株。实验结果提示敲除SHO1基因后会导致生物膜的形成能力下降。结论成功构建了白念珠菌SHO1基因敲除株,SHO1基因的敲除使白念珠菌的生物膜生成能力降低,致病力下降。展开更多
基金funded by 2023 Chongqing medical scientific research project(Joint project of Chongqing Health Commission and Science and Technology Bureaugrant no.2023GGXM006)+12 种基金oint project of Chongqing Health Commission and Science and Technology Bureau(Joint Key Laboratory Open Project)(No.2026KFXM051)Natural Science Foundation of Chongqing(No.CSTB2025NSCO-GPX1116)2026 Chongqing Municipal Health Commission Traditional Chinese Medicine Research Project(No.2026WSJK158),Technological Innovation Project of Shapingba District,Chongqing(No.2025016)2024 Scientific research project of Chongqing Medical and Pharmaceutical College(No.ygzrc2024101)Chongqing Municipal Education Commission Youth Project(No.KJQN202402821No.KJQN202502819)2024 Chongqing Medical and Pharmaceutical College Innovation Research Group Project(No.ygz2024401)Science and Health Joint Medical Research Project of Shapingba District,Chongqing(No.2024SQKWLHMS051)2025 Scientific research project of Chongqing Medical and Pharmaceutical College(No.YGZZK2025116)2025 Technological Innovation Project of Shapingba District,Chongqing(No.2025031)Chongqing Municipal Education Commission Youth Project(No.KJQN202402821No.KJQN202302811)Joint project of Chongqing Health Commission and Science and Technology Bureau(No.2024MSXM115)respectively.
文摘Host-yeast interactions are fundamental drivers of human microbiome dynamics,spanning a spectrum from mutualistic symbiosis to opportunistic pathogenesis with profound implications for systemic health.This review systematically elucidates the complex molecular mechanisms governing these relationships,with a specific focus on metabolic interdependence and immunomodulation.We analyze how yeast-derived metabolites,particularly short-chain fatty acids(SCFAs),modulate host glucose and lipid homeostasis via signaling pathways such as GPR41/43 and GLP-1 secretion.Furthermore,the review explores the pathophysiological role of fungal dysbiosis in chronic conditions,including obesity,diabetes,and inflammatory bowel disease(IBD),highlighting how a breakdown in host-yeast homeostasis triggers pro-inflammatory cascades.Beyond the fungal-host axis,we introduce the concept of the"mycobiome-virome-bacterial axis,"discussing how commensal yeasts synergize with beneficial bacteria like Bifidobacterium and influence viral infectivity through Interferon-mediated innate immune priming.We critically evaluate how cutting-edge technologies-including transgenic mouse models(specifically Dectin-1^(-/-)and CARD9^(-/-),metabolomics,and single-cell sequencing-have revolutionized our mechanistic understanding of these multi-kingdom dynamics.By integrating current findings,we identify critical knowledge gaps and propose high-resolution research frameworks,such as humanized organ-on-a-chip systems,to simulate intricate host-microbe interactions under physiological flow conditions.This comprehensive synthesis provides a strategic foundation for developing targeted,next-generation microbiome-based interventions to restore host-yeast balance and enhance overall human health.
文摘目的探讨氟康唑对阿萨希毛孢子菌(T.asahii)蛋白质组学的影响,从蛋白层面揭示T.asahii对氟康唑胁迫的响应过程及唑类耐药机制。方法以T.asahii AS 2.2174作为研究菌株,基于微量液基稀释法测定氟康唑的最低抑菌浓度(MIC)。应用串联质谱标签(TMT)技术结合液相色谱与串联质谱(LC-MS/MS)技术检测氟康唑(1×MIC)处理前后T.asahii蛋白丰度的变化。以差异倍数≥1.20或≤0.83,且P<0.05作为筛选标准,鉴定差异表达蛋白(DEPs)。对DEPs进行Gene Ontlogy(GO)和京都基因与基因组百科全书(KEGG)富集分析,以了解DEPs的生物学属性以及DEPs参与的主要生物学通路。最后,使用多反应监测(MRM)技术对目标差异蛋白进行靶向验证。结果氟康唑对T.asahii AS 2.2174的MIC值为8μg/ml。共鉴定到DEPs 196个,其中上调DEPs 93个,下调DEPs 103个。功能富集分析提示DEPs主要参与甾醇合成与代谢、药物代谢、应激反应、能量代谢及翻译等生物学过程。目标差异蛋白在MRM靶向验证和TMT-LC-MS/MS检测中具有一致的表达趋势。结论在氟康唑胁迫下,T.asahii蛋白丰度发生显著改变。生物信息学分析揭示了T.asahii响应氟康唑胁迫的复杂分子机制,这些机制对于了解T.asahii唑类耐药性及挖掘新的药物靶点提供了重要见解。
文摘目的真菌的细胞膜上普遍存在高渗透压信号蛋白1(high osmolarity signaling protein 1,Sho1),其结构相对保守,在致病机制中发挥重要作用。然而,Sho1蛋白对白念珠菌致病能力的影响尚未见报道。因此,建立构建白念珠菌SHO1基因敲除株的方法,为后续深入探索Sho1蛋白对白念珠菌生物学性状及致病能力的影响提供了理论基础。方法基因敲除技术选择采用SN152(His-/Leu-/Arg-)缺陷株为亲本株,运用融合PCR技术和同源互补的His和Leu质粒,目的基因可以被快速有效地敲除。通过结晶紫染色实验观察生物膜形成能力、聚苯乙烯孔板模型检测其黏附能力、革兰染色油镜观察菌丝形态,初步探索了Sho1蛋白对白念珠菌致病能力的影响。结果构建了his和融合PCR-his基因敲除盒,leu和融合PCR-leu基因敲除盒并将它们电转化到SN152中,用缺陷培养基筛选敲除株。通过PCR、琼脂糖凝胶电泳和基因测序方法验证SHO1基因敲除株。实验结果提示敲除SHO1基因后会导致生物膜的形成能力下降。结论成功构建了白念珠菌SHO1基因敲除株,SHO1基因的敲除使白念珠菌的生物膜生成能力降低,致病力下降。
