Function, essentiality, and expression of cytochrome P450 enzymes and their cognate redox partners in Mycobacterium tuberculosis: are they drug targets?
Antibiotic exposure response
Cytochrome P450
Essentiality
Mycobacterium tuberculosis
Redox partners
Stress response
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
30
11
2018
accepted:
10
02
2019
revised:
08
02
2019
pubmed:
28
2
2019
medline:
14
8
2019
entrez:
28
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30810776
doi: 10.1007/s00253-019-09697-z
pii: 10.1007/s00253-019-09697-z
pmc: PMC6469627
doi:
Substances chimiques
Antitubercular Agents
0
Bacterial Proteins
0
Cytochrome P-450 Enzyme System
9035-51-2
Types de publication
Journal Article
Review
Langues
eng
Pagination
3597-3614Références
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