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Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?

This review covers the current knowledge of the cytochrome P450 enzymes (CYPs) of the human pathogen Mycobacterium tuberculosis (Mtb) and their endogenous redox partners, focusing on their biological function, expression, regulation, involvement in antibiotic resistance, and suitability for exploita...

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Detalles Bibliográficos
Autores principales: Ortega Ugalde, Sandra, Boot, Maikel, Commandeur, Jan N. M., Jennings, Paul, Bitter, Wilbert, Vos, J. Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469627/
https://www.ncbi.nlm.nih.gov/pubmed/30810776
http://dx.doi.org/10.1007/s00253-019-09697-z
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author Ortega Ugalde, Sandra
Boot, Maikel
Commandeur, Jan N. M.
Jennings, Paul
Bitter, Wilbert
Vos, J. Chris
author_facet Ortega Ugalde, Sandra
Boot, Maikel
Commandeur, Jan N. M.
Jennings, Paul
Bitter, Wilbert
Vos, J. Chris
author_sort Ortega Ugalde, Sandra
collection PubMed
description This review covers the current knowledge of the cytochrome P450 enzymes (CYPs) of the human pathogen Mycobacterium tuberculosis (Mtb) and their endogenous redox partners, focusing on their biological function, expression, regulation, involvement in antibiotic resistance, and suitability for exploitation as antitubercular targets. The Mtb genome encodes twenty  CYPs and nine associated redox partners required for CYP catalytic activity. Transposon insertion mutagenesis studies have established the (conditional) essentiality of several of these enzymes for in vitro growth and host infection. Biochemical characterization of a handful of Mtb CYPs has revealed that they have specific physiological functions in bacterial virulence and persistence in the host. Analysis of the transcriptional response of Mtb CYPs and redox partners to external insults and to first-line antibiotics used to treat tuberculosis showed a diverse expression landscape, suggesting for some enzymes a potential role in drug resistance. Combining the knowledge about the physiological roles and expression profiles indicates that, at least five Mtb CYPs, CYP121A1, CYP125A1, CYP139A1, CYP142A1, and CYP143A1, as well as two ferredoxins, FdxA and FdxC, can be considered promising novel therapeutic targets.
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spelling pubmed-64696272019-05-03 Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets? Ortega Ugalde, Sandra Boot, Maikel Commandeur, Jan N. M. Jennings, Paul Bitter, Wilbert Vos, J. Chris Appl Microbiol Biotechnol Mini-Review This review covers the current knowledge of the cytochrome P450 enzymes (CYPs) of the human pathogen Mycobacterium tuberculosis (Mtb) and their endogenous redox partners, focusing on their biological function, expression, regulation, involvement in antibiotic resistance, and suitability for exploitation as antitubercular targets. The Mtb genome encodes twenty  CYPs and nine associated redox partners required for CYP catalytic activity. Transposon insertion mutagenesis studies have established the (conditional) essentiality of several of these enzymes for in vitro growth and host infection. Biochemical characterization of a handful of Mtb CYPs has revealed that they have specific physiological functions in bacterial virulence and persistence in the host. Analysis of the transcriptional response of Mtb CYPs and redox partners to external insults and to first-line antibiotics used to treat tuberculosis showed a diverse expression landscape, suggesting for some enzymes a potential role in drug resistance. Combining the knowledge about the physiological roles and expression profiles indicates that, at least five Mtb CYPs, CYP121A1, CYP125A1, CYP139A1, CYP142A1, and CYP143A1, as well as two ferredoxins, FdxA and FdxC, can be considered promising novel therapeutic targets. Springer Berlin Heidelberg 2019-02-27 2019 /pmc/articles/PMC6469627/ /pubmed/30810776 http://dx.doi.org/10.1007/s00253-019-09697-z Text en © The Author(s) 2019 OpenAccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Mini-Review
Ortega Ugalde, Sandra
Boot, Maikel
Commandeur, Jan N. M.
Jennings, Paul
Bitter, Wilbert
Vos, J. Chris
Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?
title Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?
title_full Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?
title_fullStr Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?
title_full_unstemmed Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?
title_short Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?
title_sort function, essentiality, and expression of cytochrome p450 enzymes and their cognate redox partners in mycobacterium tuberculosis: are they drug targets?
topic Mini-Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469627/
https://www.ncbi.nlm.nih.gov/pubmed/30810776
http://dx.doi.org/10.1007/s00253-019-09697-z
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