Infectious-bacteria-killing molecular machines have been taught to view their duty in a new manner.
Bacteria-killing nanoscale drills have been produced. These new molecular machines are triggered by visible light and can punch holes in bacteria cell membranes in less than two minutes. Because bacteria have no natural defenses against this process, it may be a viable treatment option for antibiotic-resistant bacteria.
The most recent version of Rice University's nanoscale drills is operated by visible light rather than ultraviolet (UV), as in previous generations. These have also been shown to be efficient in killing germs in real-life illnesses.
Rice scientist James Tour and his colleagues successfully tested six molecular machine variations. In as little as two minutes, they all punched holes in the membranes of gram-negative and gram-positive bacteria. For microorganisms with no natural defenses against mechanical intruders, resistance proved fruitless. That means they're unlikely to acquire resistance, which means they might be used to combat germs that have developed resistance to regular antibiotic treatments over time.
“I tell students that when they are my age, antibiotic-resistant bacteria are going to make COVID look like a walk in the park,” Tour added. “Antibiotics won’t be able to keep 10 million people a year from dying of bacterial infections. But this really stops them.”
The groundbreaking research conducted by Tour and Rice grads Ana Santos and Dongdong Liu will be published in the journal Science Advances today (June 1, 2022).
The Rice lab has been perfecting its molecules for years since prolonged exposure to UV can be harmful to people. The new version obtains its energy from 405 nanometer light, which spins the molecules' rotors at a rate of 2 to 3 million times per second.
Other studies have shown that light at that wavelength has weak antibacterial capabilities on its own, but adding molecular machinery boosts it, according to Tour, who believes that bacterial diseases like those encountered by burn patients and persons with gangrene would be the first targets.
The machines are based on Nobel Laureate Bernard Feringa's work in 1999, when he created the first molecule with a rotor and got it to spin dependably in one direction. In a 2017 Nature piece, Tour and his colleagues described their advanced drills.
The novel compounds' capacity to kill bacteria swiftly was validated in the Rice lab's first experiments on burn wound infection models, including methicillin-resistant Staphylococcus aureus, a frequent cause of skin and soft tissue infections that killed over 100,000 people in 2019.
By adding a nitrogen group, the team was able to accomplish visible light activation. “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 amines of the machines and the negatively charged bacterial membrane,” said Liu, who is now a scientist at Arcus Biosciences in California.
The robots also break up biofilms and persister cells, which go dormant to escape antibacterial treatments, according to the researchers.
“Even if an antibiotic kills most of a colony, there are often a few persister cells that for some reason don’t die,” Tour said. “But that doesn’t matter to the drills.”
The new devices, like previous iterations, claim to resurrect antibacterial medications that have been deemed useless. “Drilling through the microorganisms’ membranes allows otherwise ineffective drugs to enter cells and overcome the bug’s intrinsic or acquired resistance to antibiotics,” said Santos, who is in her third year of a postdoctoral global fellowship that brought her to Rice for two years and is now continuing at the Health Research Institute of the Balearic Islands in Palma, Spain.
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