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

Year: 2024

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Pseudomonas aeruginosa 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 P. aeruginosa infections are available. Here, we present the noninvasive pathogen-specific detection of P. aeruginosa 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 P. aeruginosa biofilms in vitro . Importantly, for the targeting of LecA an activity boost to low-nanomolar affinity could be achieved, which is essential for in vivo application. In vitro, 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 P. aeruginosa infections and suggest their potential as pathogen-specific diagnostics to accelerate the start of the appropriate treatment.

Source: JACS Au

DOI: 10.1021/jacsau.4c00670