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    Antibiotic-functionalized gold nanoparticles for the detection of active beta-lactamases

    Year: 2022

    Journal: Nanoscale Adv., Volume 4, JAN 18, page 573–581

    Authors: Miller, Lisa M.; Simmons, Matthew D.; Silver, Callum D.; Krauss, Thomas F.; Thomas, Gavin H.; Johnson, Steven D.; Duhme-Klair, Anne-Kathrin

    Organizations: Multiparameter Assay for Profiling Susceptibility (MAPS) grant, EPSRC [EP/P02324X/1]; Research England's Connecting Capability Fund [CCF11-7795]; EPSRC [EP/P02324X/1] Funding Source: UKRI

    Antimicrobial resistance (AMR) continues to threaten the effective treatment and prevention of bacterial infections. The spread of resistant infections is accelerated by the lack of fast and cost-effective tests for the detection of AMR at the point-of-care. We aimed to address this challenge by developing a diagnostic tool to detect one of the major forms of AMR, the beta-lactamase enzymes. Antibiotic-functionalized gold nanoparticles (AuNPs) have been successfully developed for the detection of beta-lactamases in challenging biological media, namely undiluted urine. Furthermore, these tools are compatible with samples containing a urine sample preservative (boric acid) or hematuria (blood). The functionalized AuNPs interact with the active beta-lactamases, resulting in the hydrolysis of the surface-bound antibiotics, which then inhibits binding of the AuNPs to a capture protein (a penicillin-binding protein) to indicate the presence of active beta-lactamases. We successfully integrated the antibiotic-functionalized AuNPs into a new lateral flow assay (LFA), which can be used to detect active beta-lactamases down to the detection limit of 11 nM. While we demonstrate the use of antibiotic-functionalized AuNPs in an LFA format to provide a novel method of detecting active beta-lactamases, these functionalized AuNPs are amenable to a range of alternative diagnostic technologies and could lead to vital point-of-care diagnostics for the early detection of multi-drug resistant infections.
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