Nitric oxide-mediated regulation of Aspergillus flavus asexual development by targeting TCA cycle and mitochondrial function

• Published in: Journal of hazardous materials 2024-06, Vol.471, p.134385-134385, Article 134385
• Main Authors: Yang, Kunlong, Luo, Yue, Sun, Tongzheng, Qiu, Han, Geng, Qingru, Li, Yongxin, Liu, Man, Keller, Nancy P., Song, Fengqin, Tian, Jun
• Format: Article
• Language: English
• Subjects: Aconitase; Aflatoxin; Aspergillus flavus; Nitric oxide; TCA cycle
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.134385

Nitric oxide (NO) is a signaling molecule with diverse roles in various organisms. However, its role in the opportunistic pathogen Aspergillus flavus remains unclear. This study investigates the potential of NO, mediated by metabolites from A. oryzae (AO), as an antifungal strategy against A. flavus. We demonstrated that AO metabolites effectively suppressed A. flavus asexual development, a critical stage in its lifecycle. Transcriptomic analysis revealed that AO metabolites induced NO synthesis genes, leading to increased intracellular NO levels. Reducing intracellular NO content rescued A. flavus spores from germination inhibition caused by AO metabolites. Furthermore, exogenous NO treatment and dysfunction of flavohemoglobin Fhb1, a key NO detoxification enzyme, significantly impaired A. flavus asexual development. RNA-sequencing and metabolomic analyses revealed significant metabolic disruptions within tricarboxylic acid (TCA) cycle upon AO treatment. NO treatment significantly reduced mitochondrial membrane potential (Δψm) and ATP generation. Additionally, aberrant metabolic flux within the TCA cycle was observed upon NO treatment. Further analysis revealed that NO induced S-nitrosylation of five key TCA cycle enzymes. Genetic analysis demonstrated that the S-nitrosylated Aconitase Acon and one subunit of succinate dehydrogenase Sdh2 played crucial roles in A. flavus development by regulating ATP production. This study highlights the potential of NO as a novel antifungal strategy to control A. flavus by compromising its mitochondrial function and energy metabolism. [Display omitted] ●oryzae metabolites inhibit A. flavus development by inducing NO production.●NO disrupts A. flavus mitochondrial function and TCA metabolism.●NO induces S-nitrosylation of key TCA enzymes.●Aconitase and Succinate dehydrogenase are crucial targets for NO-mediated antifungal activity.