Escherichia coli RNA polymerase is the target of the cyclopeptide antibiotic microcin J25

Escherichia coli microcin J25 (MccJ25) is a plasmid-encoded, cyclic peptide antibiotic consisting of 21 unmodified amino acid residues. It is primaril y active on gram-negative bacteria related to the producer strain, inducing cell filamentation in an SOS-independent way. A mutation causing resistanc e to MccJ25 was isolated. Genetic analysis indicated that it resided in the rpoC gene, encoding the beta ' subunit of RNA polymerase, at 90 min on the E. coli genetic map, The mutation was genetically crossed on to a plasmid containing the wild-type rpoC gene. The presence of the recombinant plasmid conferred complete resistance to otherwise sensitive strains. Nucleotide s equencing of the plasmid-borne, mutant rpoC gene revealed a ACC (Thr)-to-AT C (Ile) change at codon 931, within homology block G, an evolutionarily con served region in the large subunits of all RNA polymerases. MccJ25 decrease d RNA synthesis both in vivo and in vitro. These results point to the RNA p olymerase as the target of microcin action. We favor the possibility that t he filamentous phenotype induced by MccJ25 results from impaired transcript ion of genes coding for cell division proteins. As far as we know, MccJ25 i s the first peptide antibiotic shown to affect RNA polymerase.