Doxycycline-Decorated Silver Nanoparticle-Based Plasmon-Enhanced Fluorescence Nanoplatform for Accurate Prediction of Antibiotic Susceptibility against Superbugs

Antibiotic-resistant superbugs are a global threat that are predicted to become the leading cause of death worldwide. To effectively combat superbugs, accurate prediction of antibiotic susceptibility is crucial, which takes more than 24 h in clinics now. Herein, we report doxycycline (DX) antibiotic-decorated silver nanoparticle (AgNP)-based plasmonic metal-enhanced fluorescence (PMEF) nanoplatforms for accurate, rapid, and sensitive prediction of antibiotic susceptibility against different superbugs. Using time-resolved emission and three-dimensional finite-difference time domain (3D-FDTD) simulation data, we show that due to the plasmonic coupling between neighboring AgNPs in "hotspots", very low fluorescence signals from DX can be enhanced ∼75 times via enhancing the higher rate of excitation and radiative decay rates. We show that in the presence of different bacterial strains, depending on the doxycycline antibiotic susceptibility, the antibiotics are released from the plasmon surface and change PMEF intensity, which can be used for determining antibiotic susceptibility against superbugs. Experimental data indicate a huge change of PMEF intensity in the presence of MRSA, demonstrating that the antibiotic susceptibility for doxycycline antibiotics is very good for MRSA. However, there is no change of PMFE intensity in the presence of <i>Salmonella DT104</i> or carbapenem-resistant <i>Escherichia coli</i> strain, indicating that the antibiotic susceptibility of DX is very poor against those superbugs. Colony counting and LIVE/DEAD <i>Bac</i>Light Bacterial Viability Kit data confirmed the observed PMEF results. We show that within 30 min, PMFE can determine the susceptibility of doxycycline antibiotics against different superbugs. Reported data indicate that the PMFE sensitivity for DX susceptibility testing can be as low as 50 CFU/mL MRSA superbugs. The current report shows the potential of DX-AgNP-based PMEF for rapid and accurate diagnosis of antibiotic susceptibility for superbugs.