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Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. | LitMetric

AI Article Synopsis

  • - Mycobacterial species thrive in sphagnum peat bogs, where they compete for nutrients with various microorganisms, including fungi.
  • - Researchers tested fungi from these bogs against Mycobacterium tuberculosis (Mtb) and found five fungi that produce agents capable of killing Mtb upon exposure.
  • - Whole genome sequencing and RNA sequencing revealed that three fungi produced patulin, one produced citrinin, and another produced a previously unreported compound, nidulalin A, all of which cause significant stress to Mtb by targeting thiols.

Article Abstract

Mycobacterial species in nature are found in abundance in sphagnum peat bogs where they compete for nutrients with a variety of microorganisms including fungi. We screened a collection of fungi isolated from sphagnum bogs by co-culture with Mycobacterium tuberculosis (Mtb) to look for inducible expression of antitubercular agents and identified 5 fungi that produced cidal antitubercular agents upon exposure to live Mtb. Whole genome sequencing of these fungi followed by fungal RNAseq after Mtb exposure allowed us to identify biosynthetic gene clusters induced by co-culture. Three of these fungi induced expression of patulin, one induced citrinin expression and one induced the production of nidulalin A. The biosynthetic gene clusters for patulin and citrinin have been previously described but the genes involved in nidulalin A production have not been described before. All 3 of these potent electrophiles react with thiols and treatment of Mtb cells with these agents followed by Mtb RNAseq showed that these natural products all induce profound thiol stress suggesting a rapid depletion of mycothiol. The induction of thiol-reactive mycotoxins through 3 different systems in response to exposure to Mtb suggests that fungi have identified this as a highly vulnerable target in a similar microenvironment to that of the caseous human lesion.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614215PMC
http://dx.doi.org/10.1371/journal.pbio.3002852DOI Listing

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