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Membranes of infectious bacteria are not suitable for molecular devices

The membranes of infectious bacteria do not match the molecular machines developed at Rice University. The machines are activated by visible light and pierce the bacteria, killing them. Exercise could also destroy the evolved resistance of microorganisms to antibiotics, allowing drugs to enter. Credit: Tour 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 do not have a natural defense against this mechanism, it could be a useful strategy to treat antibiotic-resistant bacteria.

The latest iteration of nanoscale drilling developed at Rice University is activated by visible light rather than ultraviolet (UV), as in previous versions. They have also been shown to be effective in killing bacteria by testing for actual infections.

Six variants of molecular machines have been successfully tested by Rice chemist James Tour and his team. They all made holes in the membranes of gram-negative and gram-positive bacteria in just two minutes. Resistance has been useless for bacteria that do not have a natural defense against mechanical invaders. This means that they are unlikely to develop resistance, potentially providing 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 will not be able to stop 10 million people a year from dying from bacterial infections. But that really stops them. ”

Escherichia coli bacteria after exposure to light-activated molecular drilling

An image with a transmission electron microscope shows Escherichia coli bacteria in various stages of degradation after exposure to light-activated molecular drilling developed at Rice University. The devices are capable of piercing the membranes of antibiotic-resistant bacteria, killing them in minutes. Credit: Image by Matthew Meyer / Rice University

The revolutionary study led by Tour and Rice graduates Ana Santos and Dongdong Liu will be published today (June 1, 2022) in the journal Advances in science.

Because prolonged UV exposure can be harmful to humans, Rice’s lab has been refining its molecules for years. The new version gets its energy from the still bluish light at 405 nanometers, rotating the rotors of the molecules 2 to 3 million times per second.

Other researchers have suggested that light at that wavelength has mild antibacterial properties, but the addition of molecular machines overpowers it, said Tour, who suggested that bacterial infections such as burns and gangrene will be early targets.

The machines are based on the Nobel Prize-winning work of Bernard Feringa, who developed the first rotor molecule in 1999 and made the rotor rotate reliably in one direction. Tour and his team presented their advanced exercises in 2017 The nature paper.

Schemes of molecular machines that kill bacteria

The diagrams show two variants of light-activated molecular machines developed at Rice University that drill and destroy antibiotic-resistant bacteria. The devices may be useful in the fight against infectious skin diseases. Credit: Tour Research Group / Rice University

Early tests by Rice Lab with new molecules on burn wound infection models confirmed their ability to kill bacteria quickly, including methicillin-resistant Staphylococcus aureus, a common cause of skin and soft tissue infections that has been responsible for more of 100,000 deaths in 2019.

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

Researchers have also found that the devices effectively destroy biofilms and persistent cells, which become latent to avoid antibacterial drugs.

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

As with previous versions, the new devices also promise to revive antibacterial drugs that are considered ineffective. “Drilling through the membranes of microorganisms allows otherwise ineffective drugs to enter the cells and overcome the intrinsic or acquired resistance of the virus to antibiotics,” said Santos, who is in his third year at the Global Postdoctoral Fellowship. for two years and continues. at the Balearic Islands Health Research Institute in Palma, Spain.

The lab is working on better targeting of bacteria to minimize damage to mammalian cells by binding bacterial-specific peptide labels to boreholes to target them to pathogens of interest. “But even without that, the peptide can be applied in a place of bacterial concentration, as in a burn area,” Santos said.

Reference: “Light-activated molecular machinery is a fast-acting broad-spectrum membrane-targeting antibacterial” June 1, 2022, Advances in science.
DOI: 10.1126 / sciadv.abm2055

Co-authors are Rice Anna Reed and John Li, senior Aaron Wyderka, Alexis van Venrooy and Jacob Beckham graduates, Victor Li researcher, Mikita Misiura and Olga Samoylova postdoctoral graduates, Ciceron Ayala-Orozco researcher, Lawrence Alemany lecturer and Anatoly Kolomeisky, professor 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 a professor of chemistry at TT and WF Chao and a 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.

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