Anu Taila, an herbal nasal-drop, delays spore germination in Cunninghamella bertholletiae by reducing cAMP-PKA dependent ROS in mucorale pathogen and extrinsic ROS in human host cells

The rare, fastest-germinating, frequently invasive mucorale, Cunninghamella bertholletiae, is intractable due to its imprecise etiology. Cunninghamella bertholletiae spores can infect both immunocompromised and immunocompetent individuals to cause mucormycosis. Sub-optimal drug-susceptibility further limits its treatment options. The classical nasal drop, Anu Taila, is reported to be effective against the rather prevalent mucorales, Mucor spp., making its anti-mucormycotic effect against C. bertholletiae worth testing. The inhibitory effect of Anu Taila against C. bertholletiae was manifested as microstructural alterations of the spores and their delayed germination. Anu Taila reduced the germination-promoting reactive oxygen species (ROS) levels in both the pathogen, C. bertholletiae, and the human host lung epithelial A549 cells. Expressions of structural (chitin synthase, trehalose synthase) and functional (cAMP-PKA) markers of spore germination were regulated by Anu Taila. cAMP-PKA expression and ROS generation are well-correlated, implicating the role of Anu Taila in delaying C. bertholletiae spore germination by targeting cAMP-PKA-mediated ROS generation. In conclusion, this study demonstrates that Anu Taila can create an opportunity for the host immune system to tackle the onset of C. bertholletiae infection by delaying its pathogenesis. This can be further leveraged to reinforce the host immune system through combinatorial treatment to prevent the establishment of the mucormycosis infection.