小柯机器人

美国布朗大学Richard J. Bennett和德国汉斯·克诺尔研究所(HKI)Bernhard Hube共同合作，近期取得重要工作进展。他们研究提出，菌丝特异性毒素念珠菌素能够促进真菌肠道共生。相关研究成果2024年3月6日在线发表于《自然》杂志上。

据介绍，真菌白色念珠菌经常定植于人类胃肠道，并可从中传播引起全身性疾病。这种多态性物种可以在生长为单细胞酵母和多细胞菌丝之间转换，以适应其环境。目前白色念珠菌共生的理论认为，酵母形式对肠道定植是最佳的，而菌丝细胞对定植是有害的，但对毒力至关重要。

研究人员发现这种模式并不适用于多界群落，其中真菌形态和细菌之间的复杂相互作用决定了白色念珠菌的适应性。因此，当肠道细菌不存在或被抗生素耗尽时，酵母锁定的细胞胜过野生型细胞，而在细菌种群充足的宿主中，菌丝感受态野生型细胞胜过酵母锁定细胞。野生型细胞适应度的增加涉及菌丝特异性因子的产生，包括促进定植建立的毒素念珠菌溶素。在以后的时间点，适应性免疫参与，肠道免疫球蛋白A优先选择对抗菌丝细胞。因此，菌丝形态类型在肠道中处于正选择性压力和负选择性压力下。

总之，这一研究进一步表明，念珠菌溶血素对细菌有直接的抑制作用，包括限制它们的代谢输出。因此，研究人员提出，白色念珠菌已经演化出菌丝特异性因子，包括念珠菌溶素，以更好地与肠道生态位中的细菌物种竞争。

附：英文原文

Title: The hyphal-specific toxin candidalysin promotes fungal gut commensalism

Author: Liang, Shen-Huan, Sircaik, Shabnam, Dainis, Joseph, Kakade, Pallavi, Penumutchu, Swathi, McDonough, Liam D., Chen, Ying-Han, Frazer, Corey, Schille, Tim B., Allert, Stefanie, Elshafee, Osama, Hnel, Maria, Mogavero, Selene, Vaishnava, Shipra, Cadwell, Ken, Belenky, Peter, Perez, J. Christian, Hube, Bernhard, Ene, Iuliana V., Bennett, Richard J.

Issue&Volume: 2024-03-06

Abstract: The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence1,2,3. Here, we reveal that this paradigm does not apply to multi-kingdom communities in which a complex interplay between fungal morphology and bacteria dictates C. albicans fitness. Thus, whereas yeast-locked cells outcompete wild-type cells when gut bacteria are absent or depleted by antibiotics, hyphae-competent wild-type cells outcompete yeast-locked cells in hosts with replete bacterial populations. This increased fitness of wild-type cells involves the production of hyphal-specific factors including the toxin candidalysin4,5, which promotes the establishment of colonization. At later time points, adaptive immunity is engaged, and intestinal immunoglobulin A preferentially selects against hyphal cells1,6. Hyphal morphotypes are thus under both positive and negative selective pressures in the gut. Our study further shows that candidalysin has a direct inhibitory effect on bacterial species, including limiting their metabolic output. We therefore propose that C. albicans has evolved hyphal-specific factors, including candidalysin, to better compete with bacterial species in the intestinal niche.

DOI: 10.1038/s41586-024-07142-4

Source: https://www.nature.com/articles/s41586-024-07142-4

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