Glyoxal oxidase-mediated detoxification of reactive carbonyl species contributes to virulence, stress tolerance, and development in a pathogenic fungus

• Published in: PLoS pathogens 2024-07, Vol.20 (7), p.e1012431
• Main Authors: Liu, Xiaoyu, Keyhani, Nemat O, Liu, Hong, Zhang, Yue, Xia, Yuxian, Cao, Yueqing
• Format: Article
• Language: English
• Subjects: Alcohol Oxidoreductases - genetics; Alcohol Oxidoreductases - metabolism; Aldehydes; Amino acids; Animals; Apoptosis; Appressoria; Autophagy; Biodegradation; Carbonyl compounds; Carbonyls; Carboxylic acids; Cell membranes; Cell walls; Chemical properties; Cuticles; Damage tolerance; Detoxification; Enzymes; Epicuticle; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; Fungi, Pathogenic; Gene disruption; Germination; Growth; Hydrogen peroxide; Immune system; Immunological tolerance; Infections; Insects; Lignin; Lignocellulose; Lipid metabolism; Lipid peroxidation; Lipids; Localization; Metabolic conjugation; Metarhizium - genetics; Metarhizium - metabolism; Metarhizium - pathogenicity; Metarhizium acridum; Microbiological research; Mutants; Nucleic acids; Osmotic stress; Oxidases; Oxidative Stress; Pathogenicity; Pathogens; Penetration resistance; Physiological aspects; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Scavenging; Stress (Physiology); Stress, Physiological; Toxicity; Transcriptomics; Virulence; Virulence (Microbiology)
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012431

Reactive carbonyl and oxygen species (RCS/ROS), often generated as metabolic byproducts, particularly under conditions of pathology, can cause direct damage to proteins, lipids, and nucleic acids. Glyoxal oxidases (Gloxs) oxidize aldehydes to carboxylic acids, generating hydrogen peroxide (H2O2). Although best characterized for their roles in lignin degradation, Glox in plant fungal pathogens are known to contribute to virulence, however, the mechanism underlying such effects are unclear. Here, we show that Glox in the insect pathogenic fungus, Metarhizium acridum, is highly expressed in mycelia and during formation of infection structures (appressoria), with the enzyme localizing to the cell membrane. MaGlox targeted gene disruption mutants showed RCS and ROS accumulation, resulting in cell toxicity, induction of apoptosis and increased autophagy, inhibiting normal fungal growth and development. The ability of the MaGlox mutant to scavenge RCS was significantly reduced, and the mutant exhibited increased susceptibility to aldehydes, oxidative and cell wall perturbing agents but not toward osmotic stress, with altered cell wall contents. The ΔMaGlox mutant was impaired in its ability to penetrate the host cuticle and evade host immune defense resulting in attenuated pathogenicity. Overexpression of MaGlox promoted fungal growth and conidial germination, increased tolerance to H2O2, but had little to other phenotypic effects. Transcriptomic analyses revealed downregulation of genes related to cell wall synthesis, conidiation, stress tolerance, and host cuticle penetration in the ΔMaGlox mutant. These findings demonstrate that MaGlox-mediated scavenging of RCS is required for virulence, and contributes to normal fungal growth and development, stress resistance.