Evidence for Widespread Class II Microcins in Enterobacterales Genomes

T. Jeffrey Cole, Jennifer K. Parker, Aaron Lee Feller, Claus O Wilke, Bryan W. Davies

Abstract:

Microcins are a class of antimicrobial peptides produced by certain
Gram-negative bacterial species to kill or inhibit the growth of competing bacteria.
Only 10 unique, experimentally validated class II microcins have been identified, and
the majority of these come from Escherichia coli. Although the current representation
of microcins is sparse, they exhibit a diverse array of molecular functionalities, uptake
mechanisms, and target specificities. This broad diversity from such a small representa-
tion suggests that microcins may have untapped potential for bioprospecting peptide
antibiotics from genomic data sets. We used a systematic bioinformatics approach to
search for verified and novel class II microcins in E. coli and other species within its
family, Enterobacteriaceae. Nearly one-quarter of the E. coli genome assemblies con-
tained one or more microcins, where the prevalence of hits to specific microcins varied
by isolate phylogroup. E. coli isolates from human extraintestinal and poultry meat
sources were enriched for microcins, while those from freshwater were depleted.
Putative microcins were found in various abundances across all five distinct phylogenetic
lineages of Enterobacteriaceae, with a particularly high prevalence in the “Klebsiella” clade.
Representative genome assemblies from species across the Enterobacterales order, as well
as a few outgroup species, also contained putative microcin sequences. This study sug-
gests that microcins have a complicated evolutionary history, spanning far beyond our
limited knowledge of the currently validated microcins. Efforts to functionally characterize
these newly identified microcins have great potential to open a new field of peptide anti-
biotics and microbiome modulators and elucidate the ways in which bacteria compete
with each other.