Multi-drug-resistant (MDR) bacteria are becoming a severe threat to public health. Some well-known examples of these superbugs are MRSA, or methicillin-resistant Staphylococcus aureus, Escherichia coli, Salmonella enterica and Klebsiella pneumoniae. These bacteria are responsible for a host of life-threatening hospital- and community-acquired infections that are often very difficult to treat.

Researchers led by Anushree Chatterjee and Prashant Nagpal have now found that the activity of existing antibiotics can be boosted by the presence of semiconducting nanoparticles, or quantum dots, which, when activated with light, produce reactive oxygen species known as superoxides.

“MDR bacteria have genetically evolved to overcome the stress they experience when exposed to antibiotics. When we expose them to a dose of superoxides at the same time, however, the bacteria need to divert their resources to overcome the new superoxide stress,” explains Nagpal. “This then makes them more vulnerable to the antibiotic itself.”

Quantum-dot treatment works with a range of different antibiotics

The experiments by the researchers on bacteria-infected worms and infected human cells show that the quantum-dot treatment works with a range of different antibiotics that are ineffective against superbugs. “We have tested our therapy on a variety of different gram positive and gram negative bacteria, from E. coli to Salmonella and MRSA, that have varying degrees of antibiotic resistance (some are resistant to two or more drugs, for example, while other really potent stains are resistant to more than 20 antibiotics),” says Chatterjee.

“We also looked at a range of lab strains to patient clinical isolates and found that the treatment works for all the tested pathogens, even at antibiotic concentrations that are up to 1000 times lower than those normally required. We did not see any cases where it didn’t work, but the main difference was the dose required to kill such or such a strain.”

The quantum dots have the advantage of being able to work at the intracellular level, where many bacteria grow and reproduce, she adds. The dots can enter cells and help clear up the infection from within.

Extending to the infrared

“Although we are still a long way from clinical trials, and there is still much work to do, we hope that these quantum dots could be taken at the same time as antibiotics (either intravenously or through an aerosol),” she tells nanotechweb.org. “For the actual treatment, the patient could be asked to sit in a bright room, for example, or outside in the sun to activate the particles. Alternatively, she or he could wear clothing lined with light-emitting diodes emitting visible light.”

The team, reporting its work in Science Advances DOI: 10.1126/sciadv.1701776, says that it is now busy designing different materials for making the quantum dots, and especially those that absorb in the near-infrared part of the electromagnetic spectrum (rather than just the visible). Infrared light penetrates deeper into biological tissue, so these dots might be used to clear up infections in deep tissue or bone.

“We are also looking to design quantum dots that generate a range of selective radicals (other than superoxides) that do not harm host mammalian cells but which can clear antibiotic-resistant infections,” says Nagpal. “Our goal is to develop a whole gamut of inexpensive and efficient antibiotic therapies against resistant superbugs. We can produce gram quantities of the quantum dots quickly and at an astonishingly low price and the treatment only requires nanomolar concentrations to work.

“Ultimately, we need to keep a few steps ahead of these fast-evolving, and, might I say, smart bugs. New therapies like ours will hopefully give us a fighting chance in an evolutionary race we can’t afford to lose.”