Uropathogenic Escherichia coli adhesins (UPEC adhesins)

Uropathogenic Escherichia coli (UPEC) adhesins are specialized surface proteins that facilitate the attachment of bacteria to the host urinary tract epithelium, representing a critical initial step in the development of urinary tract infections (UTIs) (Terlizzi et al., 2017, Frontiers in Microbiology). The most prominent member of this group is FimH, a mannose-binding lectin located at the tip of type 1 pili, which anchors the bacteria to uroplakin proteins on bladder cells (Sauer et al., 2019, Nature Communications). Other adhesins, such as PapG on P-pili, mediate colonization of the upper urinary tract, including the kidneys, by binding to specific glycolipid receptors (Terlizzi et al., 2017). By enabling stable adhesion, these molecules allow UPEC to resist being flushed out by urine flow and promote the formation of intracellular bacterial communities and biofilms (Spaulding et al., 2017, Nature). Therapeutic targeting of these adhesins, particularly through small-molecule FimH antagonists like Sibofimloc or GSK3882347, aims to prevent bacterial colonization without the selective pressure for resistance associated with traditional antibiotics (ClinicalTrials.gov, NCT03943446). These anti-adhesion agents work by competitively occupying the binding pockets of the adhesins, thereby neutralizing the pathogen's ability to infect host tissues (Sauer et al., 2019).

Other names

FimHPapGSfaSDraEType 1 pilus adhesinP-pilus adhesinDr adhesinAfa adhesinFimH adhesin

Competitive inhibition of the lectin domain of bacterial adhesins (primarily FimH) to prevent binding to host cell surface receptors such as uroplakins or glycolipids, thereby blocking bacterial attachment and colonization (Sauer et al., 2019; Spaulding et al., 2017).