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

Applied Microbiology and Biotechnology
Sandra Ortega UgaldeJ Chris Vos

Abstract

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 consider...Continue Reading

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Citations

Jun 26, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Luiz G F LopesEduardo H S Sousa
Jan 25, 2020·Molecular Medicine Reports·Rui-Ying WangXiao-Bing Shen
Oct 15, 2019·Frontiers in Genetics·Dixit SharmaShailender Kumar Verma
Jul 28, 2019·Microbiology Spectrum·Gabriel T MashabelaDigby F Warner

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