Mechanistic aspects of 1-methyl-4-phenyl pyridinium iodide toxicity in Escherichia coli: The role of oxygen and hydrogen peroxide

1-Methyl-4-phenyl pyridinium iodide (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 Escherichia coli model and demonstrated that MPP⁺ is toxic to bacterial cells in dose- and time-dependent modes. Additionally, it is shown that only in the presence of molecular oxygen did bacterial inactivation occur. This requirement for oxygen can be circumvented by adventitious H₂O₂. 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.