Deadly "Superbugs" Destroyed By Molecular Drills

Molecular drills have been given the ability to control and destroy deadly bacteria that have developed resistance to almost all antibiotics. In some cases, the drills make the antibiotics effective again.

Researchers from Rice University, Texas A&M University, Biola University, and Durham (UK) University have shown that motorized molecules developed in the chemist James Tour's Rice Lab can kill antibiotic-resistant microbes in a matter of minutes.

"These superbugs could kill 10 million people a year by 2050, overtaking cancer," Tour said. "These are nightmare bacteria; they don't respond to anything."

The motors target the bacteria and, as soon as they are activated with light, dig through the outside.

While bacteria can develop to resist antibiotics by locking out the antibiotics, the bacteria have no defense against molecular drills. Antibiotics that can get through the drill holes are deadly again for the bacteria.

The researchers reported their findings in the American Chemical Society's journal ACS Nano.

Tour and Robert Pal, a research fellow from the Royal Society University in Durham and co-author of the new paper, presented the molecular drillings for piercing cells in 2017. The drills are paddle-like molecules that can be made to spin at 3 million revolutions per second when activated with light.

Tests by the Texas A&M laboratory of the leading scientist Jeffrey Cirillo and the former rice researcher Richard Gunasekera in Biola killed Klebsiella pneumoniae within a few minutes. Microscopic images of bacteria showed where motors had drilled through cell walls.

"Bacteria don't just have a lipid bilayer," Tour said. "They have two double layers and proteins with sugar that bind them together so that things don't normally get through these very robust cell walls. That's why these bacteria are so difficult to kill. But they have no way of standing up against a machine like these molecules To defend." Drill as this is a mechanical and not a chemical effect. "

The engines also increased K. pneumonia's susceptibility to meropenem, an antibacterial drug to which the bacteria had developed resistance. "Sometimes when the bacterium detects a drug, it doesn't let it in," Tour said. "Other times, bacteria defeat the drug by taking it in and deactivating it."

He said Meropenem is an example of the former. "Now we can get it through the cell wall," said Tour. "This can breathe new life into ineffective antibiotics when used in combination with the molecular drills."

According to Gunasekera, bacterial colonies with a low concentration of nanomachines alone killed up to 17% of the cells, but these increased to 65% with the addition of meropenem. After a further balance between motor skills and antibiotics, the researchers were able to kill 94% of the pneumonia pathogen.

According to the tour, the nanomachines could have an immediate effect in treating skin, wound, catheter or implant infections caused by bacteria such as Staphylococcus aureus MRSA, Klebsiella or Pseudomonas and intestinal infections. "We can attack these bacteria on the skin, lungs, or gastrointestinal tract wherever we can insert a light source," he said. "Or you could let the blood flow through a light-containing external box and then back into the body to kill blood-borne bacteria."

"We are very interested in treating wound and implant infections," said Cirillo. "However, we have ways to deliver these wavelengths of light to lung infections that cause numerous deaths from pneumonia, cystic fibrosis, and tuberculosis. That's why we're going to develop respiratory infections."

Gunasekera found that bladder-borne bacteria that cause urinary tract infections can also be affected.

The article is one of two articles published by the Tour Laboratory this week that improve the ability of microscopic nanomachines to treat diseases. In the other, which appears in ACS Applied Materials Interfaces, researchers from Rice and the University of Texas' MD Anderson Cancer Center have examined and attacked laboratory samples of pancreatic cancer cells using devices that respond to visible rather than previously used ultraviolet light. "This is another big step forward because visible light doesn't damage the surrounding cells as much," Tour said.

Journal Reference:

Thushara Galbadage, Dongdong Liu, Lawrence B. Alemany, Robert Pal, James M. Tour, Richard S. Gunasekera, Jeffrey D. Cirillo. Molecular Nanomachines Disrupt Bacterial Cell Wall, Increasing Sensitivity of Extensively Drug-Resistant Klebsiella pneumoniae to Meropenem. ACS Nano, 2019; DOI: 10.1021/acsnano.9b07836