Ec W: A Novel Narrow-Spectrum Class IIb Microcin from Escherichia coli

The rise of antimicrobial-resistant infections highlights the need for novel therapeutic strategies. Class IIb microcins, a subclass of ribosomally synthesized bacteriocins, play a significant role in modulating bacterial communities by targeting iron acquisition systems in competitive environments, such as the gastrointestinal tract. In this study, we describe and characterize Ec W, a novel class IIb microcin from Escherichia coli strain NCTC10444. This strain is the first known to harbor two homologs of the class IIb microcin biosynthesis cluster and to encode four class IIb microcins in its genome. Sequence analysis revealed that Ec W shows similarity to class IIb microcin Gq W, extending the known repertoire of this microcin class to 18. Heterologous expression and inhibition assays demonstrated potent antimicrobial activity of Ec W against numerous enteric pathogens from the Enterobacteriaceae family, including drug-resistant and hypervirulent strains of E. coli and Klebsiella pneumoniae. These findings suggest that Ec W holds substantial promise as an antimicrobial agent, providing a potential alternative to traditional antibiotics for combating multidrug-resistant pathogens. This study emphasizes the importance of exploring microcins as a novel strategy to tackle the growing threat of infections caused by multidrug-resistant bacteria.