High-Affinity Lectin Ligands Enable the Detection of Pathogenic <i>Pseudomonas aeruginosa</i> Biofilms: Implications for Diagnostics and Therapy

<i>Pseudomonas aeruginosa</i> is a critical priority pathogen and causes life-threatening acute and biofilm-associated chronic infections. The choice of suitable treatment for complicated infections requires lengthy culturing for species identification from swabs or an invasive biopsy. To date, no fast, pathogen-specific diagnostic tools for <i>P. aeruginosa</i> infections are available. Here, we present the noninvasive pathogen-specific detection of <i>P. aeruginosa</i> using novel fluorescent probes that target the bacterial biofilm-associated lectins LecA and LecB. Several glycomimetic probes were developed to target these extracellular lectins and demonstrated to stain <i>P. aeruginosa</i> biofilms <i>in vitro</i>. Importantly, for the targeting of LecA an activity boost to low-nanomolar affinity could be achieved, which is essential for <i>in vivo</i> application. <i>In vitro</i>, the nanomolar divalent LecA-targeted imaging probe accumulated effectively in biofilms under flow conditions, independent of the fluorophore identity. Investigation of these glycomimetic imaging probes in a murine lung infection model and fluorescence imaging revealed accumulation at the infection site. These findings demonstrate the use of LecA- and LecB-targeting probes for the imaging of <i>P. aeruginosa</i> infections and suggest their potential as pathogen-specific diagnostics to accelerate the start of the appropriate treatment.