Structure of microcin B-like compounds produced by Pseudomonas syringae and species specificity of their antibacterial action

J Bacteriol. 2013 Sep;195(18):4129-37. doi: 10.1128/JB.00665-13. Epub 2013 Jul 12.

Abstract

Escherichia coli microcin B (Ec-McB) is a posttranslationally modified antibacterial peptide containing multiple oxazole and thiazole heterocycles and targeting the DNA gyrase. We have found operons homologous to the Ec-McB biosynthesis-immunity operon mcb in recently sequenced genomes of several pathovars of the plant pathogen Pseudomonas syringae, and we produced two variants of P. syringae microcin B (Ps-McB) in E. coli by heterologous expression. Like Ec-McB, both versions of Ps-McB target the DNA gyrase, but unlike Ec-McB, they are active against various species of the Pseudomonas genus, including human pathogen P. aeruginosa. Through analysis of Ec-McB/Ps-McB chimeras, we demonstrate that three centrally located unmodified amino acids of Ps-McB are sufficient to determine activity against Pseudomonas, likely by allowing specific recognition by a transport system that remains to be identified. The results open the way for construction of McB-based antibacterial molecules with extended spectra of biological activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteriocins / biosynthesis
  • Bacteriocins / chemistry*
  • Bacteriocins / genetics
  • Bacteriocins / pharmacology*
  • Cloning, Molecular
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Humans
  • Operon
  • Pseudomonas / classification
  • Pseudomonas / drug effects*
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas syringae / chemistry*
  • Pseudomonas syringae / genetics
  • Pseudomonas syringae / metabolism*
  • Species Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tandem Mass Spectrometry
  • Topoisomerase II Inhibitors*

Substances

  • Anti-Bacterial Agents
  • Bacteriocins
  • Topoisomerase II Inhibitors
  • microcin