Molecular basis of resistance to cytochrome bc(1) inhibitors

Fisher, Nicholas and Meunier, B. (2008) 'Molecular basis of resistance to cytochrome bc(1) inhibitors'. Fems Yeast Research, Vol 8, Issue 2, pp. 183-192.

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Abstract

Inhibitors of the mitochondrial respiratory chain enzyme cytochrome bc(1) (respiratory complex III) have been developed as antimicrobial agents. They are used in agriculture to control plant pathogenic fungi and in medicine against human pathogens, such as the malaria parasite Plasmodium falciparum, or Pneumocystis jiroveci (an opportunistic pathogenic fungus life-threatening in immuno-compromised patients). These respiratory inhibitors are thus effective against a broad range of important pathogens. Unfortunately, the problem of acquired resistance has rapidly emerged. A growing number of pathogen isolates resistant to inhibitor treatment have been reported, and this resistance is often linked to mutation within cytochrome b, one of the essential catalytic subunits of the complex. Saccharomyces cerevisiae is an invaluable model in order to assess the impact of the mutations on the sensitivity to the drugs, on the respiratory capacity and the fitness of cells. In this minireview, the inhibitors, their mode of action, and the mutations implicated in resistance and studied in yeast are briefly reviewed. Four mutations that are of particular importance in medicine and in agriculture are briefly reviewed and described in more detail and the molecular basis of resistance and of evolution of the mutations is discussed succinctly.

Item Type:	Article
Additional Information:	The definitive version is available at www3.interscience.wiley.com
Uncontrolled Keywords:	cytochrome b fungicides resistance respiratory chain saccharomyces-cerevisiae atovaquone-resistance q-cycle electron-transfer b mutations c reductase q(o) site ubiquinol oxidation mutants resistant toxoplasma-gondii
Subjects:	QX Parasitology > Protozoa > QX 135 Plasmodia QY Clinical Pathology > Blood. Blood Chemistry > QY 450 Blood chemistry WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 190 Hemoglobin and other hemeproteins. Porphyrins (Associated with hemoglobin)
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1111/j.1567-1364.2007.00328.x
Depositing User:	Mary Creegan
Date Deposited:	19 Aug 2010 12:54
Last Modified:	06 Feb 2018 13:00
URI:	https://archive.lstmed.ac.uk/id/eprint/777

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