RNA polymerase is the primary target of microcin J25 in Salmonella enterica serovar Newport

LACHENICHT, JA; SALOMÓN, RA; ARIAS, VJ

Córdoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The main target of the peptide antibiotic microcin J25 (MccJ25) in Escherichia coli is the RNA polymerase. It has been suggested that the antibiotic might have a different mode of action on Salmonella Newport. In this study, we determined the frequency of selection of spontaneous resistance to MccJ25 in S. Newport. One hundred and fifty MccJ25-insensitive colonies were picked up. As in E. coli, mutations conferring resistance resided in fhuA, tonB, exbB, exbD, and sbmA genes. In only one of the mutants, transformation with a plasmid harboring the E. coli rpoB and rpoC genes fully reversed the MccJ25 resistance phenotype. This result indicated that this mutant possess a change in the RNA polymerase. The fact that the mutation confers complete resistance to high concentrations of MccJ25 suggests that inhibition of the polymerase alone accounts for its antibacterial activity on S. Newport. The mutation frequency of resistance to MccJ25 in S. Newport was 5 x 10?7 (number of mutants per total number of viable bacteria). The high propensity of MccJ25 for selection of resistance in vitro could limit interest for development as a future drug candidate, especially for monotherapy. However, if derivatives of MccJ25 with improved features can be developed, these could be a source of novel drug leads.