Pathogen adherence sites on mucosal surfaces

Pathogen adherence sites on mucosal surfaces are the molecular interfaces where pathogens initiate infection by binding to host epithelial cells. These sites comprise a heterogeneous group of receptors, including glycans (e.g., sialic acid, heparan sulfate) and proteins (e.g., integrins, CEACAMs), which are exploited by bacteria, viruses, and fungi for colonization [Nature Reviews Microbiology, 2004]. In drug development, these sites are the focus of anti-adhesion therapy, a strategy designed to prevent the first step of pathogenesis without necessarily killing the microbe, thereby minimizing selective pressure for resistance [Frontiers in Cellular and Infection Microbiology, 2020]. Current pharmacological approaches include the use of decoy receptors, such as human milk oligosaccharides, and monoclonal antibodies like Palivizumab, which sterically hinder the interaction between pathogen adhesins and their mucosal targets [Journal of Clinical Investigation, 2013]. This target class is critical for addressing infections at the portal of entry, particularly in the respiratory and gastrointestinal tracts [NCBI, 2021]. By blocking these initial interactions, therapeutics can effectively reduce the pathogen burden and prevent the progression to systemic disease. Furthermore, targeting host-side receptors can sometimes provide a broader spectrum of activity against multiple pathogens that share the same binding motif.

Other names

Mucosal adhesion receptorsHost cell attachment sitesEpithelial adhesion receptorsPathogen docking sites

Competitive inhibition of pathogen-host binding by mimicking host receptors (decoy receptors) or masking pathogen adhesins to prevent colonization [Nature Reviews Microbiology, 2004].