Molecular Nanomachines Boldly Go Where Many Antibiotics Can’t

Antibiotic-resistant pathogens have had their deadly way with some chemical-based drugs, but they don’t seem to hold the same power to resist, dodge, or defeat machines the size of molecules. Investigators with Rice University, Texas A&M University, Biola University, and Durham in the United Kingdom say that motorized molecules can drill into the pathogens and kill them within minutes. Not only that, but in some cases the drills make the antibiotics effective again, according to a new study published in ACS Nano.

Bacteria are well-defended by 2 bilayers and proteins with sugars that interlink them. Rice lab chemist James Tour points out in a press release that “things don’t normally get through these very robust cell walls. That’s why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect.”

The ability of bacteria to evolve and resist antibiotics cannot protect them from these light-activated molecular nanomachines (MNM1s). “This is because bacterial antimicrobial resistance mechanisms are not developed against a nanomechanical agent that disrupts bacterial cell walls,” the study states, adding that the MNM1s’ paddlelike molecules can spin at 3 million rotations per second. “We have shown the ability of light-activated MNM1 to disrupt cell walls by its nanomechanical action….”

The investigators state that the motors aid meropenem, an antibacterial drug that fights Klebsiella pneumoniae and which has built up a resistance to the drug. 

“This gram-negative opportunistic pathogen colonizes the human intestine and is of high clinical importance, especially among very sick patients,” the study states.

In addition to pneumonia, K. pneumoniae can cause bloodstream infections, urinary tract infections, wound or surgical site infections, and meningitis.

The drill enables the meropenem to get through the cell wall and get to work. A small number of MNN1s helped kill up to 17% of K. pneumonia cells, according to the study, but that jumped to 65% when they were used in concert with meropenem. Investigators were able to kill 94% of the pneumonia-causing pathogens when they further tinkered with the balance between the MNM1s and meropenem.

The MNM1s will most likely see action in treating skin, wound, catheter, or implant-causing infections caused by methicillin-resistant Staphylococcus aureus (MRSA), Klebsiellaor Pseudomonas, according to the study.

“On the skin, in the lungs or in the GI tract, wherever we can introduce a light source, we can attack these bacteria,” Tour said. “Or one could have the blood flow through a light-containing external box and then back into the body to kill blood-borne bacteria.”

Texas A&M lab lead scientist Jeffrey Cirillo said in the press release that “we have ways to deliver these wavelengths of light to lung infections that cause numerous mortalities from pneumonia, cystic fibrosis, and tuberculosis, so we will also be developing respiratory infection treatments.”