MccJ25 induces an irreversible damage of mitochondrial lipids and proteins by oxygen and nitrogen reactive species overproduction

NIKLISON CHIROU, M. V.; ARCURI, B.; CARLOS JAVIER MINAHK; DUPUY, F. G.; BELLOMIO, A.; MORERO, R. D.

La Plata, Buenos Aires

Congreso; XXXVII Reunión Anual de la Sociedad Argentina de Biofísica; 2008

Sociedad Argentina de Biofísica

Microcin J25, a 21-amino acid antimicrobial peptide produced by an Escherichia coli strain, is active against close-related bacteria including certain human pathogens as some Salmonella and Shigella strains. The peptide has an unusual lasso distinctive structure and it is bacteriostatic agent in E. coli by inhibiting RNA polymerase causing an impaired transcription of genes encoding cell division proteins. An alternative mechanism of action has been described on Salmonella serovar Newport cells. It was demonstrated that this antibiotic disrupts membrane integrity and therefore causes a dissipation of the membrane electrical potential in Salmonella serovar Newport cells. Furthermore, MccJ25 inhibits NADH and succinate dehydrogenase and alters the oxygen consumption rate.In addition, an superoxide anion production was described in E. coli. We previously showed that the antimicrobial peptide microcin J25 induced the over-production of reactive oxygen species with the concomitant release of cytochrome c from rat heart mitochondria via the opening of the mitochondrial permeability transition pore. Here, we were able to demonstrate that indeed, as a consequence of the oxidative burst, MccJ25 induces carbonylation of mitochondrial proteins, which may explain the irreversible inhibition of complex III and the partial inhibition of superoxide dismutase and catalase. Moreover, the peptide raised the levels of oxidized membrane lipids, which triggers the release of cytochrome c.