Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis.
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 expr...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-12-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002852 |
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| author | Neha Malhotra Sangmi Oh Peter Finin Jessica Medrano Jenna Andrews Michael Goodwin Tovah E Markowitz Justin Lack Helena I M Boshoff Clifton Earl Barry |
| author_facet | Neha Malhotra Sangmi Oh Peter Finin Jessica Medrano Jenna Andrews Michael Goodwin Tovah E Markowitz Justin Lack Helena I M Boshoff Clifton Earl Barry |
| author_sort | Neha Malhotra |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e4aee5fdfd19447097b8e163302b27cf |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-e4aee5fdfd19447097b8e163302b27cf2025-01-08T05:30:24ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-12-012212e300285210.1371/journal.pbio.3002852Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis.Neha MalhotraSangmi OhPeter FininJessica MedranoJenna AndrewsMichael GoodwinTovah E MarkowitzJustin LackHelena I M BoshoffClifton Earl BarryMycobacterial 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.https://doi.org/10.1371/journal.pbio.3002852 |
| spellingShingle | Neha Malhotra Sangmi Oh Peter Finin Jessica Medrano Jenna Andrews Michael Goodwin Tovah E Markowitz Justin Lack Helena I M Boshoff Clifton Earl Barry Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. PLoS Biology |
| title | Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. |
| title_full | Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. |
| title_fullStr | Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. |
| title_full_unstemmed | Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. |
| title_short | Environmental fungi target thiol homeostasis to compete with Mycobacterium tuberculosis. |
| title_sort | environmental fungi target thiol homeostasis to compete with mycobacterium tuberculosis |
| url | https://doi.org/10.1371/journal.pbio.3002852 |
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