Jesmin Rubaiya, Cary Jeffrey W, Lebar Matthew D, Majumdar Rajtilak, Gummadidala Phani M, Dias Travis, Chandler Savannah, Basu Paramita, Decho Alan W, Keller Nancy P, Chanda Anindya
Mycologics LLC, Frederick, MD, United States.
Food and Feed Safety Research Unit, USDA/ARS, Southern Regional Research Center, New Orleans, LA, United States.
Front Microbiol. 2023 Sep 8;14:1208961. doi: 10.3389/fmicb.2023.1208961. eCollection 2023.
Aflatoxins, a family of fungal secondary metabolites, are toxic and carcinogenic compounds that pose an enormous threat to global food safety and agricultural sustainability. Specifically agricultural products in African, Southeast Asian and hot and humid regions of American countries suffer most damage from aflatoxin producing molds due to the ideal climate conditions promoting their growth. Our recent studies suggest that (Vg), an estuarine bacterium non-pathogenic to plants and humans, can significantly inhibit aflatoxin biosynthesis in the producers. In this study, we investigated the mechanism underlying Vg-dependent aflatoxin inhibition using the prominent aflatoxin producer, . We show that aflatoxin inhibition upon Vg treatment was associated with fungal uptake of Vg-prodigiosin, a red pigment, which was consistently visible inside fungal hyphae during treatment. The association of prodigiosin with aflatoxin inhibition was further evident as , another prodigiosin producer, significantly inhibited aflatoxin, while non-producers like , , and did not. Also, pure prodigiosin significantly inhibited aflatoxin biosynthesis. Endocytosis inhibitors, filipin and natamycin, reduced the Vg-prodigiosin uptake by the fungus leading to a significant increase in aflatoxin production, suggesting that uptake is endocytosis-dependent. The Vg treatment also reduced hyphal fusion (>98% inhibition) and branching, which are both endosome-dependent processes. Our results, therefore, collectively support our theory that Vg-associated aflatoxin inhibition is mediated by an endocytosis-dependent uptake of Vg-prodigiosin, which possibly leads to a disruption of normal endosomal functions.
黄曲霉毒素是一类真菌次生代谢产物，是有毒且具有致癌性的化合物，对全球食品安全和农业可持续性构成巨大威胁。具体而言，非洲、东南亚以及美洲国家炎热潮湿地区的农产品受产黄曲霉毒素霉菌的损害最为严重，因为理想的气候条件促进了这些霉菌的生长。我们最近的研究表明，一种对植物和人类无致病性的河口细菌（Vg）能够显著抑制产毒菌中的黄曲霉毒素生物合成。在本研究中，我们使用著名的黄曲霉毒素产毒菌，研究了Vg依赖性黄曲霉毒素抑制的潜在机制。我们发现，用Vg处理后黄曲霉毒素受到抑制，这与真菌摄取Vg-灵菌红素（一种红色色素）有关，在处理过程中，真菌菌丝内始终可见该色素。灵菌红素与黄曲霉毒素抑制之间的关联进一步得到证实，因为另一种灵菌红素产生菌也能显著抑制黄曲霉毒素，而不产生灵菌红素的菌株，如、和则不能。此外，纯灵菌红素能显著抑制黄曲霉毒素生物合成。内吞作用抑制剂制霉菌素和游霉素可减少真菌对Vg-灵菌红素的摄取，导致黄曲霉毒素产量显著增加，这表明摄取是依赖内吞作用的。Vg处理还减少了菌丝融合（抑制率>98%）和分支，这两个过程均依赖于内体。因此，我们的研究结果共同支持了我们的理论，即Vg相关的黄曲霉毒素抑制是由Vg-灵菌红素的内吞作用依赖性摄取介导的，这可能导致正常内体功能的破坏。
