Siderophore-Microcins in Escherichia coli: Determinants of Digestive Colonization, the First Step Toward Virulence Original paper

What was reviewed?

Siderophore microcins in Escherichia coli are the focus of this mini review, which explains how these small antimicrobial peptides support digestive colonization and prepare strains for extraintestinal infection. The authors describe the genetic organization of microcin clusters on chromosomal islands, their modification with an enterobactin-derived siderophore group, and their export through an ABC transporter that uses TolC as the outer membrane channel. The review shows that these molecules mimic iron-loaded siderophores, enter competing Enterobacteriaceae through siderophore receptors, and then act as Trojan Horse toxins that disrupt inner membrane functions. It links this mechanism to the success of B2 phylogroup Escherichia coli in the gut and presents siderophore microcins as important functional markers within the intestinal microbiome.

Who was reviewed?

The review draws on work in commensal and pathogenic Escherichia coli, with a strong emphasis on B2 phylogroup strains that often carry extraintestinal virulence traits. It compares fecal isolates from healthy adults in industrialized regions, where B2 strains and microcin producers are frequent, with fecal isolates from parts of Africa, Asia, and South America, where A phylogroup strains are more common. It also discusses uropathogenic Escherichia coli from patients with urinary tract infection together with matched fecal isolates from the same hosts, which allows a direct link between the gut reservoir and urinary disease. In addition, the article includes data from probiotic and asymptomatic bacteriuria strains, such as Nissle 1917 and ABU 83972, and brief coverage of Klebsiella pneumoniae that produces microcin E492, all supported by genomic and transcriptomic analyses of microcin-related loci.

Most important findings

The review shows that siderophore microcins are enriched in B2 Escherichia coli and appear more often in uropathogenic strains than in fecal strains, which suggests that they support both colonization fitness and virulence potential. Microcins H47 and M dominate and sit on compact genomic islands with lower GC content than the core chromosome, which points to past horizontal acquisition. In many B2 strains, including uropathogenic Escherichia coli and probiotic Nissle 1917, the microcin island lies within a larger region that also carries salmochelin siderophore genes and the pks island for the genotoxin colibactin, which creates genomic economy because shared enzymes such as IroB, ClbA and ClbP serve more than one pathway.

Functionally, siderophore microcins use catecholate siderophore receptors such as FepA, Fiu, or Cir and the TonB system to cross the outer membrane of sensitive enterobacteria, then act on inner membrane targets such as the mannose permease or ATP synthase and cause loss of membrane potential and death. These actions give producer strains a decisive advantage in the iron-poor environment of the colon, where Fur-regulated systems induce both siderophores and microcins. Population data indicate that about one-third of uropathogenic Escherichia coli carry siderophore microcin genes, compared with a much smaller fraction of fecal isolates, and that these genes often co-occur with other virulence factors. Case control studies that compare urinary and rectal isolates from the same individuals show that a microcin M activity protein appears more often in urinary isolates even when classical virulence markers match, which links microcin-mediated competition in the intestine to later entry into the urinary tract.

Key implications

For clinicians, this review positions siderophore microcins as microbiome-related markers of Escherichia coli strains that combine strong intestinal persistence with a greater risk of extraintestinal disease, especially urinary tract infection. Microcins do not define acute severity in the urinary tract, but they help strains dominate the rectal reservoir and so increase the chance that these strains seed the perineum and urethra. Microbiome signature work that aims to predict infection risk should therefore include functional markers such as siderophore microcin islands together with B2 assignment and the presence of salmochelin and colibactin clusters, rather than rely on taxonomy alone. This pattern may support future risk stratification for recurrent urinary tract infection. The review also suggests a therapeutic angle, since microcin-inspired systems could guide narrow-spectrum agents that exploit siderophore receptors on target Enterobacteriaceae while they preserve much of the gut microbiota, although any strategy that involves colibactin-related islands will require careful safety assessment because of genotoxic concerns.