Visible light triggers bacteria-killing molecular drills to treat infections

The latest iteration of nanoscale drills – molecular machines that kill bacteria – are activated by visible light, instead of ultraviolet (UV) light, according to a new study in Science Advances.

Developed by chemists at Rice University in the US, the molecular machines can kill Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), in mere minutes.

They offer a potential strategy to kill antibiotic-resistant bacteria because bacteria without natural defences against mechanical invaders are unlikely to develop resistance to them.

“I tell students that when they are my age, antibiotic-resistant bacteria are going to make COVID look like a walk in the park,” says senior author James Tour, professor of chemistry, materials science and nanoengineering at Rice University. “Antibiotics won’t be able to keep 10 million people a year from dying of bacterial infections. But this really stops them.”

The latest iteration of molecular machines

These molecular machines are based on Nobel Prize–winning work by Bernard Feringa, who developed the first molecule with a rotor and got it to spin continuously in one direction in 1999.

Tour and his team have been refining these molecular machines since their 2017 Nature study and this newest version gets its energy from blue-ish visible light – with a wavelength of 405 nanometres – to spin the molecular rotor at an incredible rate of two to three million times per second.

This will allow patients to avoid extended exposure to UV light, which can be damaging to humans, during treatment.

The team achieved visible-light activation by adding a nitrogen group (amine).

“The molecules were further modified with different amines in either the stator (stationary) or the rotor portion of the molecule to promote the association between the protonated (positively charged) amines of the machines and the negatively charged bacterial membrane,” says co-lead author Dongdong Liu, now a scientist at Arcus Biosciences in California.

They also found that the machines can effectively break up bacterial biofilms and persister cells that have become tolerant to and resist treatment with an antibiotic.

“Even if an antibiotic kills most of a colony, there are often a few persister cells that for some reason don’t die,” Tour explains. “But that doesn’t matter to the drills.”

These drills also hold promise for reviving antibacterial drugs currently considered ineffective because “drilling through the microorganisms’ membranes allows otherwise ineffective drugs to enter cells and overcome the bug’s intrinsic or acquired resistance to antibiotics”, according to co-lead author Ana Santos, now a research scientist at the Health Research Institute of the Balearic Islands, Spain.

Tour’s team will continue to work to better the machine’s ability to target bacteria, and avoid mammalian cells, by linking bacteria-specific peptide tags to the drills to direct them toward pathogens.

“But even without that, the peptide can be applied to a site of bacterial concentration, like in a burn wound area,” says Santos.