Accumulation of heme biosynthetic intermediates contributes to the antibacterial action of the metalloid tellurite
| Autor: | Justin Nelson, Scott W. Simpkins, Fabián A. Cornejo, Jeff S. Piotrowski, Camilo A. Pinto, Claudio C. Vásquez, Eduardo H. Morales, Chad L. Myers, Claudia M. Muñoz-Villagrán, Hirotada Mori, Felipe A. Arenas, Roberto Luraschi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science 030106 microbiology Protoporphyrins General Physics and Astronomy Heme Microbial Sensitivity Tests Models Biological Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Biosynthesis Superoxides Drug Resistance Bacterial Escherichia coli Hydrogen peroxide Metalloids chemistry.chemical_classification Multidisciplinary Superoxide Aminolevulinic Acid Iron Deficiencies General Chemistry Antimicrobial Anti-Bacterial Agents Biosynthetic Pathways 3. Good health 030104 developmental biology chemistry Biochemistry Mutation Thiol Hydroxyl radical Tellurium Antibacterial activity Genome Bacterial |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-12 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The metalloid tellurite is highly toxic to microorganisms. Several mechanisms of action have been proposed, including thiol depletion and generation of hydrogen peroxide and superoxide, but none of them can fully explain its toxicity. Here we use a combination of directed evolution and chemical and biochemical approaches to demonstrate that tellurite inhibits heme biosynthesis, leading to the accumulation of intermediates of this pathway and hydroxyl radical. Unexpectedly, the development of tellurite resistance is accompanied by increased susceptibility to hydrogen peroxide. Furthermore, we show that the heme precursor 5-aminolevulinic acid, which is used as an antimicrobial agent in photodynamic therapy, potentiates tellurite toxicity. Our results define a mechanism of tellurite toxicity and warrant further research on the potential use of the combination of tellurite and 5-aminolevulinic acid in antimicrobial therapy. The mechanisms of action of the antibacterial metalloid tellurite are unclear. Here, the authors show that tellurite induces an accumulation of hydroxyl radical and intermediates of heme biosynthesis in E. coli, and that the heme precursor 5-aminolevulinic acid potentiates tellurite toxicity. |
| Databáze: | OpenAIRE |
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