June 7

CHEMISTS have shown that light-activated molecular machines can drill holes through gram-negative and gram-positive bacteria membranes, killing them in just two minutes. Their study suggests a new way to fight antibiotic-resistant bacteria, which have no natural resistance against mechanical invaders.

The study was published in the journal, “Science Advances, 2022”

The latest iteration of nanoscale drills developed at Rice University is activated by visible light rather than ultraviolet (UV), as in earlier versions. They have also been proven effective in killing bacteria through tests for real infections.

Six variants of the molecular machine

Six variants of the molecular machine were successfully tested by Rice chemist James Tour and his team. They all pierced the membranes of gram-negative and gram-positive bacteria within two minutes. Resistance is futile for bacteria that have no natural resistance against mechanical invaders. That means they are unlikely to develop resistance, possibly offering a strategy to defeat bacteria that have become immune to common antibacterial treatments over time.

“I tell students that when they’re my age, antibiotic-resistant bacteria will make COVID feel like walking in the park,” Tour said. “Antibiotics can’t keep 10 million people a year from dying of bacterial infections. But it really stops them.”

Because prolonged exposure to UV can harm humans, the Rice lab has been refining its molecules for years. The new version draws its energy from bluish light at 405 nanometres, which rotates the rotors of the molecules at 2 to 3 million times per second.

Other researchers have suggested that light at that wavelength has its own mild antibacterial properties, but the addition of molecular machines adds to this, says Tour, suggesting bacterial infections such as those experienced of burn victims and people with gangrene will be early targets.

Nobel Prize-winning work

The machines are based on the Nobel Prize-winning work of Bernard Feringa, who developed the first molecule with a rotor in 1999 and got the rotor to rotate reliably in one direction. Tour and his team introduced their advanced drills in a 2017 Nature paper.

Rice lab’s initial tests of the new molecules in burn wound infection models confirmed their ability to quickly kill bacteria, including methicillin-resistant Staphylococcus aureus, a common cause of skin and soft tissue infections. tissue that caused more than 100,000 deaths in 2019.

The team achieved visible light activation by adding a nitrogen group. “The molecules are further modified by different amines either in the stator (stationary) or in the rotor part of the molecule to promote the relationship between the protonated amines of the machines and the negatively charged bacterial membrane,” said Liu, now a scientist at Arcus Biosciences in California.

The researchers also discovered that the machines effectively destroyed biofilms and persistent cells, which become dormant to avoid antibacterial drugs.

“Even though an antibiotic kills most of a colony, there are usually a few persistent cells that for some reason don’t die,” Tour said. “But that doesn’t matter in drills.”

Antibacterial drugs

Like previous versions, the new machines also promise to activate antibacterial drugs deemed ineffective. “Drilling through the membranes of microorganisms allows otherwise ineffective drugs to enter the cells and overcome intrinsic or acquired resistance of the bug to antibiotics,” said Santos, who is in his third year postdoctoral. global fellowship that brought him to Rice for two years and continues. at the Health Research Institute of the Balearic Islands in Palma, Spain.

The lab is working toward better targeting of bacteria to reduce damage to mammalian cells by linking bacteria-specific peptide tags to drills to direct them towards pathogens. and interested. “But even without that, the peptide can be applied to a site of bacterial concentration, such as to a burn wound area,” Santos said. Source : ANI