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7 March 2019 Antibiotic-derived molecular probes for bacterial imaging
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Abstract
Infections caused by drug resistant bacteria poses a significant threat to global human health, with predicted annual mortality of 10 million by 2050. While much attention is focused on developing better therapies, improving diagnosis would allow for rapid initiation of optimal treatment, reducing unnecessary antibiotic use and enhancing therapeutic outcomes. There are currently no whole body imaging techniques in clinical use that are capable of specifically identifying bacterial infections. We have developed antibiotic-derived fluorescent probes that bind and illuminate either Gram-positive or Gram-negative bacteria with high specificity and selectivity over mammalian cells. Antibiotics are functionalised with an azide substituent in a position that minimises effects on antibiotic activity. These are reacted by facile 1,3-dipolar cycloaddition with alkyne-substituted imaging components such as visible or near-infrared fluorophores. The resulting adducts can be used as tools to image bacteria in vitro and in vivo. We have successfully functionalised representatives of seven major antibiotic classes. These derivatives retain antibacterial activity, and have been coupled with a range of fluorophores. Fluorescent versions of vancomycin and polymyxin B are particularly useful for specific labelling of G+ve and G-ve bacteria, respectively. Preliminary studies have now extended the visualisation component to include moieties compatible with PET imaging.
Conference Presentation
© (2019) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Mark A. Blaskovich, Wanida Phetsang, M. Rhia L. Stone, Urszula Lapinska, Stefano Pagliara, Rajiv Bhalla, and Matthew A. Cooper "Antibiotic-derived molecular probes for bacterial imaging", Proc. SPIE 10863, Photonic Diagnosis and Treatment of Infections and Inflammatory Diseases II, 1086303 (7 March 2019); https://doi.org/10.1117/12.2507329
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