Membranes of infectious bacteria are no match for the molecular machines developed at Rice University. The machines are activated by visible light and pierce the bacteria, killing them. The simulations could also break the evolved resistance of microorganisms to antibiotics by letting drugs in. Credit: Rice Research Group / Rice University
Molecular machines that kill infectious bacteria have been taught to see their mission in a new light.
New nanoscale drills have been developed that are effective in killing bacteria. These new molecular machines are activated by visible light and can pierce the cell membranes of bacteria in just two minutes. Because bacteria have no natural defenses against this mechanism, it could be a useful strategy to treat antibiotic-resistant bacteria.
The latest iteration of nanoscale simulations developed at Rice University is activated by visible light instead of ultraviolet (UV), as in previous versions. These have also been shown to be effective in killing bacteria by testing for actual infections.
Rice chemist James Tour and his team successfully tested six variants of molecular machines. They all made holes in the membranes of gram-negative and gram-positive bacteria in just two minutes. Resistance was useless for bacteria that had no natural defenses against mechanical invaders. This means that they are unlikely to develop resistance, potentially offering a strategy to defeat bacteria that have become immune to standard antibacterial treatments over time.
“I tell students that when they’re my age, antibiotic-resistant bacteria will make COVID look like a walk in the park,” Tour said. “Antibiotics can’t stop 10 million people a year from dying from bacterial infections. But that really stops them.”
A transmission electron microscope image shows the bacterium Escherichia coli in various stages of degradation after exposure to light-activated molecular simulations developed at Rice University. The machines are able to pierce the membranes of antibiotic-resistant bacteria, killing them in minutes. Credit: Image by Matthew Meyer / Rice University
The innovative study led by Tour and Rice alumni Ana Santos and Dongdong Liu will be published today (June 1, 2022) in the journal Science Advances.
Because prolonged exposure to UV can be harmful to humans, Rice Laboratory has been perfecting its molecules for years. The new version gets its light energy still bluish at 405 nanometers, rotating the rotors of the molecules 2 to 3 million times per second.
Other researchers have suggested that light at this wavelength has mild antibacterial properties, but the addition of molecular machines overloads it, said Tour, who suggested that bacterial infections such as those suffered by burn victims and people with gangrene will be the first goals.
The machines are based on the Nobel Prize-winning work of Bernard Feringa, who developed the first molecule with a rotor in 1999 and managed to rotate the rotor reliably in one direction. Tour and his team presented their advanced exercises in a 2017 Nature paper.
The diagrams show two variants of light-activated molecular machines developed at Rice University that were and destroy antibiotic-resistant bacteria. Machines could be useful in fighting infectious skin diseases. Credit: Rice Research Group / Rice University
Early tests by Rice Lab of new molecules on burn wound infection models confirmed their ability to kill bacteria quickly, including methicillin-resistant Staphylococcus aureus, a common cause of skin infections. and soft tissue that was responsible for more than 100,000 deaths in 2019.
The equipment achieved the activation of visible light by adding a nitrogen group. “The molecules were further modified with different amines in the stator (stationary) or rotor part of the molecule to promote the association between the protonated amines of the machines and the negatively charged bacterial membrane,” Liu said. now Arcus scientist. Biosciences in California.
The researchers also found that the machines effectively break down biofilms and persistent cells, which become latent to prevent antibacterial drugs.
“Even if an antibiotic kills most of a colony, there are often some persistent cells that for some reason don’t die,” Tour said. “But that doesn’t matter in the drills.”
As with previous versions, the new machines also promise to revive antibacterial drugs considered ineffective. “The perforation of the membranes of microorganisms allows otherwise ineffective drugs to enter the cells and overcome the intrinsic or acquired resistance of the error to antibiotics,” said Santos, who is in his third year. the global postdoctoral fellowship that took her to Rice for two years and continues. at the Balearic Islands Health Research Institute in Palma, Spain.
The lab is working to better target bacteria to minimize damage to mammalian cells by linking bacterium-specific peptide labels with drills to direct them to pathogens of interest. “But even without that, the peptide can be applied to a site of bacterial concentration, such as in a burn wound area,” Santos said.
Reference: “Light-activated molecular machines are broad-spectrum, fast-acting antibodies targeting the membrane” June 1, 2022, Science Advances.DOI: 10.1126 / sciadv.abm2055
Co-authors are Rice alumni Anna Reed and John Li, senior Aaron Wyderka, graduate students Alexis van Venrooy and Jacob Beckham, researcher Victor Li, former postdoctoral students Mikita Misiura and Olga Samoylova, research scientist Ciceron Ayala -Orozco, Professor Lawrence Alemany and Anatoly Kolomeisky. , professor of chemistry; Antonio Oliver from the Balearic Islands Health Research Institute and Son Espases University Hospital, Palma, Spain; and George Tegos of Tower Health, Reading, Pennsylvania.
Tour is the professor of chemistry TT and WF Chao and professor of materials science and nanoengineering.
The European Union’s Horizon 2020 research and innovation program (843116), the Discovery Institute, and the Robert A. Welch Foundation (C-2017-20190330) supported the research.