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Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport

Mechanisms for cellular detoxification of drug compounds are of significant interest in human health. Cyclosporine A (CsA) and tacrolimus (FK506) are widely known antifungal and immunosuppressive microbial natural products. However, both compounds can result in significant side effects when used as...

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Autores principales: Li, Yujie, Ren, Hui, Wang, Fanlong, Chen, Jianjun, Ma, Lian, Chen, Yang, Li, Xianbi, Fan, Yanhua, Jin, Dan, Hou, Lei, Zhou, Yonghong, Keyhani, Nemat O, Pei, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322151/
https://www.ncbi.nlm.nih.gov/pubmed/37405392
http://dx.doi.org/10.7554/eLife.79179
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author Li, Yujie
Ren, Hui
Wang, Fanlong
Chen, Jianjun
Ma, Lian
Chen, Yang
Li, Xianbi
Fan, Yanhua
Jin, Dan
Hou, Lei
Zhou, Yonghong
Keyhani, Nemat O
Pei, Yan
author_facet Li, Yujie
Ren, Hui
Wang, Fanlong
Chen, Jianjun
Ma, Lian
Chen, Yang
Li, Xianbi
Fan, Yanhua
Jin, Dan
Hou, Lei
Zhou, Yonghong
Keyhani, Nemat O
Pei, Yan
author_sort Li, Yujie
collection PubMed
description Mechanisms for cellular detoxification of drug compounds are of significant interest in human health. Cyclosporine A (CsA) and tacrolimus (FK506) are widely known antifungal and immunosuppressive microbial natural products. However, both compounds can result in significant side effects when used as immunosuppressants. The insect pathogenic fungus Beauveria bassiana shows resistance to CsA and FK506. However, the mechanisms underlying the resistance have remained unknown. Here, we identify a P4-ATPase gene, BbCRPA, from the fungus, which confers resistance via a unique vesicle mediated transport pathway that targets the compounds into detoxifying vacuoles. Interestingly, the expression of BbCRPA in plants promotes resistance to the phytopathogenic fungus Verticillium dahliae via detoxification of the mycotoxin cinnamyl acetate using a similar pathway. Our data reveal a new function for a subclass of P4-ATPases in cell detoxification. The P4-ATPases conferred cross-species resistance can be exploited for plant disease control and human health protection.
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spelling pubmed-103221512023-07-06 Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport Li, Yujie Ren, Hui Wang, Fanlong Chen, Jianjun Ma, Lian Chen, Yang Li, Xianbi Fan, Yanhua Jin, Dan Hou, Lei Zhou, Yonghong Keyhani, Nemat O Pei, Yan eLife Microbiology and Infectious Disease Mechanisms for cellular detoxification of drug compounds are of significant interest in human health. Cyclosporine A (CsA) and tacrolimus (FK506) are widely known antifungal and immunosuppressive microbial natural products. However, both compounds can result in significant side effects when used as immunosuppressants. The insect pathogenic fungus Beauveria bassiana shows resistance to CsA and FK506. However, the mechanisms underlying the resistance have remained unknown. Here, we identify a P4-ATPase gene, BbCRPA, from the fungus, which confers resistance via a unique vesicle mediated transport pathway that targets the compounds into detoxifying vacuoles. Interestingly, the expression of BbCRPA in plants promotes resistance to the phytopathogenic fungus Verticillium dahliae via detoxification of the mycotoxin cinnamyl acetate using a similar pathway. Our data reveal a new function for a subclass of P4-ATPases in cell detoxification. The P4-ATPases conferred cross-species resistance can be exploited for plant disease control and human health protection. eLife Sciences Publications, Ltd 2023-07-04 /pmc/articles/PMC10322151/ /pubmed/37405392 http://dx.doi.org/10.7554/eLife.79179 Text en © 2023, Li, Ren et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Li, Yujie
Ren, Hui
Wang, Fanlong
Chen, Jianjun
Ma, Lian
Chen, Yang
Li, Xianbi
Fan, Yanhua
Jin, Dan
Hou, Lei
Zhou, Yonghong
Keyhani, Nemat O
Pei, Yan
Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport
title Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport
title_full Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport
title_fullStr Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport
title_full_unstemmed Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport
title_short Cell detoxification of secondary metabolites by P4-ATPase-mediated vesicle transport
title_sort cell detoxification of secondary metabolites by p4-atpase-mediated vesicle transport
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322151/
https://www.ncbi.nlm.nih.gov/pubmed/37405392
http://dx.doi.org/10.7554/eLife.79179
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