RRC ID 6686
Author Garcia MX, Roberts C, Alexander H, Stewart AM, Harwood A, Alexander S, Insall RH.
Title Methanol and acriflavine resistance in Dictyostelium are caused by loss of catalase.
Journal Microbiology (Reading, Engl.)
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.
Volume 148(Pt 1)
Pages 333-40
Published 2002-1
DOI 10.1099/00221287-148-1-333
PMID 11782526
MeSH Acriflavine / pharmacology* Animals Anti-Infective Agents, Local / pharmacology* Bacterial Proteins / genetics Bacterial Proteins / metabolism Catalase / genetics Catalase / metabolism* Dictyostelium / drug effects* Dictyostelium / enzymology Dictyostelium / genetics Dictyostelium / metabolism Drug Resistance / genetics Escherichia coli Proteins* Gene Deletion Lipoproteins / genetics Lipoproteins / metabolism Membrane Transport Proteins Methanol / pharmacology* Molecular Sequence Data Protozoan Proteins / genetics Protozoan Proteins / metabolism
IF 2.151
Times Cited 9
WOS Category MICROBIOLOGY
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Cellular slime molds G00022