Nanoparticles: Helping Antibiotics Fight Superbugs

In the fight against antibiotic-resistant superbugs, a team of researchers in Colorado have developed nanoparticles that make resistant pathogens more susceptible to antibiotics.

Antibiotic resistance is one of the biggest challenges to public health today, posing a threat to global development and food security according to the World Health Organization (WHO). Bacteria that have evolved to evade antibiotic medicines have given rise to superbugs, causing an estimated 2 million illnesses and 23,000 deaths in the United States each year. Worldwide, it’s estimated that antibiotic-resistant bacteria will cause an additional 10 million deaths by the year 2050 and cost a total of $100 trillion in lost production. With few new antibiotics in the pipeline to tackle today’s hard-to-treat infections, researchers are developing new technologies and treatments to combat drug-resistant pathogens as public health officials caution against the misuse of antibiotics in medicine and agriculture.

A new study conducted by a team of University of Colorado Boulder investigators assessed the use of nanoparticle technology, which involves the use of particles just 1 to 100 nanometers in size, to fight pathogens with multidrug resistance. In their study, published in the journal Science Advances, the research team engineered light-activated nanoparticles of cadmium telluride called quantum dots. When light-activated, the particles generate superoxide that at elevated levels overwhelm bacterial defenses and interrupt their cellular processes, increasing the lethality of antibiotics during treatment.

In the absence of new antibiotics to fight drug-resistant pathogens, the research team used their engineered nanoparticles in conjunction with the antibiotics ceftriaxone, ciprofloxacin, streptomycin, clindamycin, and chloramphenicol. Each antibiotic was tested in five concentrations against multidrug-resistant isolates of Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae. They found that the superoxide produced by the nanoparticles potentiated the effect of the antibiotics, inhibiting the bacterial isolates and reducing their resistance to the drugs. When used in combination, the antibiotics and nanoparticles worked in more than 75% of the combinations tested, making each of the four isolates tested susceptible to one or more of the antibiotics.

“We’ve developed a one-two knockout punch,” said the study’s co-lead author, Prashant Nagpal, PhD, in a recent press release from CU Boulder. “The bacteria’s natural fight reaction [to the dots] actually leaves it more vulnerable.”

In their study, the researchers also modeled light penetration through human skin to determine the skin depth at which antibiotic potentiation could occur, demonstrating the potential of combination therapy with an external LED to activate the nanoparticles. This suggests that the therapy could be an effective treatment for skin infections and wound healing, the authors conclude. “We are thinking more like the bug,” said co-lead author, Anushree Chatterjee, PhD. “This is a novel strategy that plays against the infection’s normal strength and catalyzes the antibiotic instead.”

“Disease works much faster than we do,” said Dr. Chatterjee. “Medicine needs to evolve as well.” Ahead of next month’s World Antibiotic Awareness Week, a recent report from WHO noted that a serious lack of new antibiotics in development is increasing the threat of severe and deadly infections from antibiotic-resistant pathogens, including multidrug- and extensively-drug resistant strains of bacteria such as Klebsiella and E. coli. In response, WHO has teamed up with the Drugs for Neglected Diseases Initiative to create the Global Antibiotic Research and Development Partnership, aimed at funding research and development for new antibiotic treatments.