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MPP+ toxicity in E. coli under aerobic and anaerobic conditions
Y Haskel1, R Udassin, M Chevion
1Department of Cellular Biochemistry, Hebrew University, Jerusalem, Israel.
Abstract:
MPP+ and paraquat (PQ+2) are two structurally analogous and highly toxic pyridinium compounds. The mechanism of PQ+2 toxicity is best understood in the bacterial model system. While numerous studies, in a variety of systems, have indicated the causative role of free radicals and other oxygen-derived active species in PQ+2 toxicity, this question is yet unresolved in the case of MPP+. In this study we have used the E. coli model and have demonstrated that MPP+ is toxic to bacterial cells in a dose and time dependent modes. Additionally, it is shown that only in the presence of molecular oxygen, bacterial inactivation occurred. The protective effects of the chemical scavenger--mannitol--and of histidine are presented. These results are in complete accord with a free radical mechanism for MPP+ toxicity.
Insights
MPP+ toxicity in E. coli is oxygen-dependent and mediated by free radicals, similar to paraquat. This study confirms MPP+ bacterial inactivation involves reactive oxygen species, elucidated using chemical scavengers.
Area of Science:
- Toxicology
- Microbiology
- Biochemistry
Background:
- MPP+ and paraquat (PQ+2) are toxic pyridinium compounds.
- PQ+2 toxicity mechanism is understood via free radicals, but MPP+ mechanism is unclear.
- E. coli is a suitable model for studying pyridinium compound toxicity.
Purpose of the Study:
- To investigate the mechanism of MPP+ toxicity in E. coli.
- To determine if MPP+ toxicity involves free radicals.
- To compare MPP+ toxicity with PQ+2 in a bacterial model.
Main Methods:
- Utilized E. coli as a bacterial model system.
- Administered MPP+ in dose- and time-dependent manner.
- Assessed bacterial inactivation in the presence and absence of molecular oxygen.
- Employed chemical scavengers (mannitol, histidine) to identify reactive species.
Main Results:
- MPP+ exhibited dose- and time-dependent toxicity to E. coli.
- Bacterial inactivation by MPP+ required the presence of molecular oxygen.
- Mannitol and histidine demonstrated protective effects against MPP+ toxicity.
- Results align with a free radical-mediated mechanism for MPP+ toxicity.
Conclusions:
- MPP+ toxicity in E. coli is mediated by oxygen-dependent free radicals.
- The mechanism of MPP+ toxicity shares similarities with PQ+2.
- This study provides evidence for a free radical mechanism in MPP+ toxicity using a bacterial model.
