Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics1,2,3,4. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific5,6,7,8. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.
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LeClerc, J. E., Li, B., Payne, W. L. & Cebula, T. A. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 274, 1208–1211 (1996).
Chatterjee, A. et al. Convergent transcription confers a bistable switch in Enterococcus faecalis conjugation. Proc. Natl Acad. Sci. USA 108, 9721–9726 (2011).
Courtney, C. M. & Chatterjee, A. Sequence-specific peptide nucleic acid-based antisense inhibitors of TEM-1 β-Lactamase and mechanism of adaptive resistance. ACS Infect. Dis. 1, 253–263 (2015).
Global Tuberculosis Report (WHO, 2012).
Antibiotic Resistance Threats (CDC, 2013).
He, M. et al. Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nature Genet. 45, 109–113 (2013).
Chang, H.-H. et al. Origin and proliferation of multiple-drug resistance in bacterial pathogens. Microbiol. Mol. Biol. Rev. 79, 101–116 (2015).
Blair, J. M. A., Webber, M. A., Baylay, A. J., Ogbolu, D. O. & Piddock, L. J. V. Molecular mechanisms of antibiotic resistance. Nature Rev. Microbiol. 13, 42–51 (2015).
Falagas, M. E. & Bliziotis, I. A. Pandrug-resistant Gram-negative bacteria: the dawn of the post-antibiotic era? Int. J. Antimicrob. Agents 29, 630–636 (2007).
Yu, B. P. Cellular defenses against damage from reactive oxygen species. Physiol. Rev. 74, 139–162 (1994).
Thannickal, V. J. & Fanburg, B. L. Reactive oxygen species in cell signaling. Am. J. Physiol. Lung Cell. Mol. Physiol. 279, L1005–L1028 (2000).
Imlay, J. A. The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nature Rev. Microbiol. 11, 443–454 (2013).
Valko, M. et al. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39, 44–84 (2007).
Apel, K. & Hirt, H. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu. Rev. Plant Biol. 55, 373–399 (2004).
Kohanski, M. A., Dwyer, D. J., Hayete, B., Lawrence, C. A. & Collins, J. J. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130, 797–810 (2007).
Dwyer, D. J., Belenky, P. A., Yang, J. H., Macdonald, I. C. & Martell, J. D. Antibiotics induce redox-related physiological alterations as part of their lethality. Proc. Natl Acad. Sci. USA 111, E2100–E2109 (2014).
Sun, Q. C. et al. Plasmon-enhanced energy transfer for improved upconversion of infrared radiation in doped-lanthanide nanocrystals. Nano Lett. 14, 101–106 (2014).
Huang, X., El-Sayed, I. H., Qian, W. & El-Sayed, M. A. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J. Am. Chem. Soc. 128, 2115–2120 (2006).
Loo, C., Lowery, A., Halas, N., West, J. & Drezek, R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett. 5, 709–711 (2005).
Connor, E. E., Mwamuka, J., Gole, A., Murphy, C. J. & Wyatt, M. D. Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1, 325–327 (2005).
Sun, Q.-C., Ding, Y., Goodman, S. M., H.Funke, H. & Nagpal, P. Copper plasmonics and catalysis: role of electron–phonon interactions in dephasing localized surface plasmons. Nanoscale 6, 12450–12457 (2014).
Ipe, B. I., Lehnig, M. & Niemeyer, C. M. On the generation of free radical species from quantum dots. Small 1, 706–709 (2005).
Rengifo-Herrera, J. A. et al. A comparison of solar photocatalytic inactivation of waterborne E. coli using Tris (2,2′-bipyridine)ruthenium(II), Rose Bengal, and TiO2 . J. Sol. Energy Eng. 129, 135–140 (2007).
Walker, G. C. Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol. Rev. 48, 60–93 (1984).
Lu, Z., Li, C. M., Bao, H., Qiao, Y. & Toh, Y. Mechanism of antimicrobial activity of CdTe quantum dots. Langmuir 5445–5452 (2008).
Brayner, R. et al. Toxicological impact studies based on Escherichia coli bacteria in ultrafine ZnO nanoparticles colloidal medium. Nano Lett. 6, 866–870 (2006).
Medintz, I. L. & Mattoussi, H. Quantum dot-based resonance energy transfer and its growing application in biology. Phys. Chem. Chem. Phys. 11, 17–45 (2009).
Lovrić, J. et al. Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J. Mol. Med. 83, 377–385 (2005).
Cho, S. J. et al. Long-term exposure to CdTe quantum dots causes functional impairments in live cells. Langmuir 23, 1974–1980 (2007).
Breakpoint Tables for Interpretation of MICs and Zone Diameters Version 5.0 (EUCAST, 2015); http://www.eucast.org.
Singh, V., Beltran, I. J. C., Ribot, J. C. & Nagpal, P. Photocatalysis deconstructed: design of a new selective catalyst for artificial photosynthesis. Nano Lett. 14, 597–603 (2014).
We acknowledge financial support from W. M. Keck Foundation and University of Colorado startup funds, and NSF Graduate fellowship (DGE 1144083) to C.M.C. We would also like to thank T. Nahreini and S. Bryant for allowing use of their cell culture facilities.
The authors have filed a patent on this technology.
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Courtney, C., Goodman, S., McDaniel, J. et al. Photoexcited quantum dots for killing multidrug-resistant bacteria. Nature Mater 15, 529–534 (2016). https://doi.org/10.1038/nmat4542
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