Methanol and acriflavine resistance in Dictyostelium are caused by loss of catalase

Garcia, M. X. U., Roberts, C., Alexander, H., Stewart, A. M., Harwood, A., Alexander, S. and Insall, R. H. (2002) Methanol and acriflavine resistance in Dictyostelium are caused by loss of catalase. Microbiology, 148(1), pp. 333-340. (doi:10.1099/00221287-148-1-333) (PMID:11782526)

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Abstract

Various chemicals with harmful effects are not themselves toxic, but are metabolized in vivo to produce toxic products. One example is methanol in Dictyostelium, which is lethal to cells containing the acrA gene, but relatively harmless to acrA mutants. This makes methanol resistance one of the tightest genetic selections in Dictyostelium. Loss of acrA also confers cross-resistance to unrelated compounds such as acriflavine and thiabendazole. We have used insertional mutagenesis to demonstrate that the acrA locus encodes the peroxisomal catalase A enzyme. Disruption of the catA gene results in parallel resistance to acriflavine. Molecular and biochemical studies of several previously characterized methanol-resistant strains reveal that each lacks catalase activity. One allele, acrA2, contains a 13 bp deletion which introduces a frameshift in the middle of the gene. The involvement of catalase in methanol resistance in Dictyostelium compares with its role in methanol metabolism in yeast and rodents. However, this is the first study to show that catalase is required for the toxicity of acriflavine. Our results imply that acriflavine and thiabendazole are precursors which must be oxidized to generate biologically active species. The catA/acrA gene is also a potentially invaluable negative selectable marker for Dictyostelium molecular genetics.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Insall, Professor Robert
Authors: Garcia, M. X. U., Roberts, C., Alexander, H., Stewart, A. M., Harwood, A., Alexander, S., and Insall, R. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Microbiology
Publisher:Microbiology Society
ISSN:1350-0872
ISSN (Online):1465-2080
Published Online:01 January 2002

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