Accumulation of heme biosynthetic intermediates contributes to the antibacterial action of the metalloid tellurite
نویسندگان
چکیده
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.
منابع مشابه
The Thiol:Disulfide Oxidoreductase DsbB Mediates the Oxidizing Effects of the Toxic Metalloid Tellurite (TeO3
متن کامل
Antimicrobial and Antioxidant Activity of the Biologically Synthesized Tellurium Nanorods; A Preliminary In vitro Study
Background: Recent theranostic (therapeutic or diagnostic) applications of tellurium nanoparticles have attracted a great interest for development of different methods for synthesis of this valuable nanostructure, especially via biological resources. Objectives: In the present study, the antimicrobial and antioxidant effects of the tellurium nanorods (Te NRs) biosynthesized by a bacterial...
متن کاملIsolation of tellurite- and selenite-resistant bacteria from hydrothermal vents of the Juan de Fuca Ridge in the Pacific Ocean.
Deep-ocean hydrothermal-vent environments are rich in heavy metals and metalloids and present excellent sites for the isolation of metal-resistant microorganisms. Both metalloid-oxide-resistant and metalloid-oxide-reducing bacteria were found. Tellurite- and selenite-reducing strains were isolated in high numbers from ocean water near hydrothermal vents, bacterial films, and sulfide-rich rocks....
متن کاملBacteriochlorophyll and heme synthesis in Rhodopseudomonas spheroides: possible role of heme in regulation of the branched biosynthetic pathway.
Synthesis of heme, measured by incorporation of iron-59, and of bacteriochlorophyll was studied with wild-type and mutant strains of Rhodopseudomonas spheroides. The wild type formed heme from glycine and succinate at one-fortieth the rate of bacteriochlorophyll under anaerobic-light conditions. Added delta-aminolevulinate stimulated heme synthesis 10-fold without increasing bacteriochlorophyll...
متن کاملSelenite Protection of Tellurite Toxicity Toward Escherichia coli
In this work the influence of selenite on metal resistance in Escherichia coli was examined. Both synergistic and antagonistic resistance and toxicities were found upon co exposure with selenite. In wild type cells co-exposure to selenite had little effect on arsenic resistance, decreased resistance to cadmium and mercury but led to a dramatically increased resistance to tellurite of 32-fold. D...
متن کامل