| RRC ID |
50608
|
| Author |
Morales EH, Pinto CA, Luraschi R, Muñoz-Villagrán CM, Cornejo FA, Simpkins SW, Nelson J, Arenas FA, Piotrowski JS, Myers CL, Mori H, Vásquez CC.
|
| Title |
Accumulation of heme biosynthetic intermediates contributes to the antibacterial action of the metalloid tellurite.
|
| Journal |
Nat Commun
|
| Abstract |
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.
|
| Volume |
8
|
| Pages |
15320
|
| Published |
2017-5-11
|
| DOI |
10.1038/ncomms15320
|
| PII |
ncomms15320
|
| PMID |
28492282
|
| PMC |
PMC5437285
|
| MeSH |
Aminolevulinic Acid / pharmacology
Anti-Bacterial Agents / pharmacology*
Biosynthetic Pathways* / drug effects
Drug Resistance, Bacterial / drug effects
Escherichia coli / drug effects
Escherichia coli / genetics
Escherichia coli / metabolism
Genome, Bacterial
Heme / biosynthesis*
Iron Deficiencies
Metalloids / pharmacology*
Microbial Sensitivity Tests
Models, Biological
Mutation / genetics
Protoporphyrins / pharmacology
Superoxides / metabolism
Tellurium / pharmacology*
Tellurium / toxicity
|
| IF |
12.121
|
| Times Cited |
9
|
| Resource |
| Prokaryotes E. coli |
BW25113
JW3838-KC
JW2429-KC |
