Antimicrobial resistance (AMR) represents one of the greatest challenges facing humankind. It is currently responsible for 700,000 deaths/year. By 2050, 10 million lives/year worldwide will be at risk from drug-resistant infections.
Commonly used antibiotics are becoming increasingly ineffective against a growing number of drug-resistant pathogens and the development of new antimicrobial agents has stagnated. There is an urgent global need to develop safe and effective new antimicrobials that limit the rise of bacterial resistance.
In a recently published study, researchers have created a light-activated molecular machine that showed it can drill holes through the membranes of gram-negative and gram-positive bacteria, killing them in just minutes. The results appear in the journal Science Advances.
These synthetic molecular motors, or molecular machines (MMs), are molecular structures that can rotate unidirectionally in a controlled manner in response to stimuli, resulting in mechanical action, which in this case is light.
Using Light-Activated Molecular Machines
For the study, the team used 6 visible light-activated MMs that were able to kill gram-negative and positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), in as little as 2 minutes of light activation without detectable resistance.
The antibacterial mode of action of MMs involves physical disruption of the membrane. In addition, by permeabilizing the membrane, MMs at sublethal doses potentiate the action of conventional antibiotics.
The researchers are working toward better targeting of bacteria to minimize damage to mammalian cells by linking bacteria-specific peptide tags to the drills to direct them toward pathogens of interest.
Ana L. Santos, et al. Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane. Science Advances, 2022; 8 (22) DOI: 10.1126/sciadv.abm2055
Rice University. “Visible light triggers molecular machines to treat infections.” ScienceDaily. ScienceDaily, 1 June 2022. <www.sciencedaily.com/releases/2022/06/220601142804.htm>.