title: Mycofumigation by the volatile organic compound-producing Fungus Muscodor albus induces bacterial cell death through DNA damage.
abstract: Muscodor albus belongs to a genus of endophytic fungi that inhibit and kill other fungi, bacteria, and insects through production of a complex mixture of volatile organic compounds (VOCs). This process of mycofumigation has found commercial application for control of human and plant pathogens, but the mechanism of the VOC toxicity is unknown. Here, the mode of action of these volatiles was investigated through a series of genetic screens and biochemical assays. A single-gene knockout screen revealed high sensitivity for Escherichia coli lacking enzymes in the pathways of DNA repair, DNA metabolic process, and response to stress when exposed to the VOCs of M. albus. Furthermore, the sensitivity of knockouts involved in the repair of specific DNA alkyl adducts suggests that the VOCs may induce alkylation. Evidence of DNA damage suggests that these adducts lead to breaks during DNA replication or transcription if not properly repaired. Additional cytotoxicity profiling indicated that during VOC exposure, E. coli became filamentous and demonstrated an increase in cellular membrane fluidity. The volatile nature of the toxic compounds produced by M. albus and their broad range of inhibition make this fungus an attractive biological agent. Understanding the antimicrobial effects and the VOC mode of action will inform the utility and safety of potential mycofumigation applications for M. albus.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
authors.forename: Cambria J
authors.initials: CJ
authors.lastname: Alpha
authors.affiliation: Microbial Diversity Institute, Department of Molecular, Cellular and Developmental Biology, and Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Campos
authors.affiliation: Microbial Diversity Institute, Department of Molecular, Cellular and Developmental Biology, and Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Jacobs-Wagner
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA scott.strobel@yale.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Strobel
mesh_terms: D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D053960:DNA Breaks / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D005651:Fumigation / Q000379:methods*; D050296:Microbial Viability / Q000187:drug effects*; D010572:Pest Control, Biological / Q000379:methods; D055549:Volatile Organic Compounds / Q000378:metabolism / Q000494:pharmacology*; D013098:Xylariales / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D055549:Volatile Organic Compounds; D004247:DNA