High-Affinity Lectin Ligands Enable the Detection of Pathogenic Pseudomonas aeruginosa Biofilms: Implications for Diagnostics and Therapy
2
Issued Date
2024-01-01
Resource Type
eISSN
26913704
Scopus ID
2-s2.0-85211074344
Journal Title
JACS Au
Rights Holder(s)
SCOPUS
Bibliographic Citation
JACS Au (2024)
Suggested Citation
Zahorska E., Denig L.M., Lienenklaus S., Kuhaudomlarp S., Tschernig T., Lipp P., Munder A., Gillon E., Minervini S., Verkhova V., Imberty A., Wagner S., Titz A. High-Affinity Lectin Ligands Enable the Detection of Pathogenic Pseudomonas aeruginosa Biofilms: Implications for Diagnostics and Therapy. JACS Au (2024). doi:10.1021/jacsau.4c00670 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/102353
Title
High-Affinity Lectin Ligands Enable the Detection of Pathogenic Pseudomonas aeruginosa Biofilms: Implications for Diagnostics and Therapy
Author's Affiliation
Faculty of Science, Mahidol University
Universität des Saarlandes
Hannover Medical School
Universitätsklinikum des Saarlandes Medizinische Fakultät der Universität des Saarlandes
Helmholtz Centre for Infection Research (HZI)
Centre de Recherches sur les Macromolécules Végétales
German Center for Lung Research
Deutsches Zentrum für Infektionsforschung (DZIF)
Universität des Saarlandes
Hannover Medical School
Universitätsklinikum des Saarlandes Medizinische Fakultät der Universität des Saarlandes
Helmholtz Centre for Infection Research (HZI)
Centre de Recherches sur les Macromolécules Végétales
German Center for Lung Research
Deutsches Zentrum für Infektionsforschung (DZIF)
Corresponding Author(s)
Other Contributor(s)
Abstract
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.