High-Affinity Lectin\nLigands Enable the Detection\nof Pathogenic Pseudomonas aeruginosa Biofilms: Implications for Diagnostics and Therapy

Pseudomonas\naeruginosa is a critical\npriority pathogen and causes life-threatening acute and biofilm-associated\nchronic infections. The choice of suitable treatment for complicated\ninfections requires lengthy culturing for species identification from\nswabs or an invasive biopsy. To date, no fast, pathogen-specific diagnostic\ntools for P. aeruginosa infections\nare available. Here, we present the noninvasive pathogen-specific\ndetection of P. aeruginosa using novel\nfluorescent probes that target the bacterial biofilm-associated lectins\nLecA and LecB. Several glycomimetic probes were developed to target\nthese extracellular lectins and demonstrated to stain P. aeruginosa biofilms <i>in vitro</i>.\nImportantly, for the targeting of LecA an activity boost to low-nanomolar\naffinity could be achieved, which is essential for <i>in vivo</i> application. <i>In vitro</i>, the nanomolar divalent LecA-targeted\nimaging probe accumulated effectively in biofilms under flow conditions,\nindependent of the fluorophore identity. Investigation of these glycomimetic\nimaging probes in a murine lung infection model and fluorescence imaging\nrevealed accumulation at the infection site. These findings demonstrate\nthe use of LecA- and LecB-targeting probes for the imaging of P. aeruginosa infections and suggest their potential\nas pathogen-specific diagnostics to accelerate the start of the appropriate\ntreatment.