Molecular drills can target and destroy deadly bacteria that have evolved resistance to nearly all antibiotics—and in some cases can even make the antibiotics effective again, a new study shows.
Researchers showed that the motorized molecules can kill antibiotic-resistant microbes within minutes.
“These superbugs could kill 10 million people a year by 2050, way overtaking cancer,” says James Tour of Rice University. “These are nightmare bacteria; they don’t respond to anything.”
The motors target the bacteria and, once activated with light, burrow through their exteriors.
While bacteria can evolve to resist antibiotics by locking the antibiotics out, they have no defense against molecular drills. Antibiotics able to get through openings the drills make become lethal to bacteria once again.
The findings appear in ACS Nano.
Researchers introduced the molecular drills for boring through cells in 2017. The drills are paddlelike molecules that researchers can prompt to spin at 3 million rotations per second when activated with light.
In tests, the drills effectively killed Klebsiella pneumoniae within minutes. Microscopic images of targeted bacteria showed where motors had drilled through cell walls.
“Bacteria don’t just have a lipid bilayer,” Tour says “They have two bilayers and proteins with sugars that interlink them, so things don’t normally get through these very robust cell walls. That’s why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect.”
The motors also increased the susceptibility of K. pneumonia to meropenem, an antibacterial drug to which the bacteria had developed resistance.
“Sometimes, when the bacteria figures out a drug, it doesn’t let it in,” Tour says. “Other times, bacteria defeat the drug by letting it in and deactivating it.”
Meropenem is an example of the former, Tour says. “Now we can get it through the cell wall. This can breathe new life into ineffective antibiotics by using them in combination with the molecular drills.”
Attack the bacteria
Bacterial colonies targeted with a small concentration of nanomachines alone killed up to 17% of cells, but that increased to 65% with the addition of meropenem, says Richard Gunasekera, formerly a researcher at Rice and now at Biola University.
After further balancing motors and the antibiotic, the researchers were able to kill 94% of the pneumonia-causing pathogen.
The nanomachines may see their most immediate impact in treating skin, wound, catheter, or implant infections caused by bacteria—like Staphylococcus aureus MRSA, klebsiella, or pseudomonas—and intestinal infections, Tour says.
“On the skin, in the lungs, or in the GI tract, wherever we can introduce a light source, we can attack these bacteria. Or one could have the blood flow through a light-containing external box and then back into the body to kill blood-borne bacteria.”
“We are very much interested in treating wound and implant infections initially,” says lead scientist Jeffrey Cirillo of Texas A&M University.
“But we have ways to deliver these wavelengths of light to lung infections that cause numerous mortalities from pneumonia, cystic fibrosis, and tuberculosis, so we will also be developing respiratory infection treatments.”
The researchers may also target bladder-borne bacteria that cause urinary tract infections, Gunasekera says.
The researchers wrote another paper that advances the ability of microscopic nanomachines to treat disease in ACS Applied Materials Interfaces.
In that paper, researchers at Rice and the University of Texas MD Anderson Cancer Center targeted and attacked lab samples of pancreatic cancer cells with machines that respond to visible rather than the previously used ultraviolet light.
“This is another big advance, since visible light will not cause as much damage to the surrounding cells,” Tour says.
Tour is a professor of chemistry and of computer science, materials science, and nanoengineering. Cirillo is a professor and director of Texas A&M’s Center for Airborne Pathogen Research and Tuberculosis Imaging. Gunasekera is associate dean of academic and research affairs of the School of Science, Technology and Health and professor of biological sciences and biochemistry at Biola. Additional coauthors are from Durham University.
The Discovery Institute, the Welch Foundation, the National Institutes of Health, the UK’s Biotechnology and Biological Sciences Research Council, and the Royal Society University Research Fellowship funded the work.
Source: Rice University