The efficacy of conventional antibiotic treatments has been on the decline for years owing to their excessive use. Antibiotic resistance is a growing concern and now poses one of the biggest threats to global health. Without alternative solutions, a post-antibiotic era in which common infections and minor injuries pose serious risks may be inevitable.
Promising emergent strategies are shifting the focus away from traditional chemical antibiotic treatments and towards physical methods, including ultraviolet radiation, gamma-rays and heating. While effective for inactivating pathogens, these techniques also cause extensive collateral damage to human tissue, making them unsuitable for clinical use.
Enter visible light. At low doses, this form of electromagnetic radiation is considered safe for human cells and blood proteins while being capable of inactivating pathogens, including bacteria and viruses.
Of particular interest are ultrashort-pulse (femtosecond) lasers. The germicidal properties of such lasers have been previously explored and demonstrate a unique ability to inactivate pathogens that are challenging to kill by other means.
In collaboration with Shelley Haydel, a professor of microbiology at Arizona State University, researchers at Washington University School of Medicine in St. Louis have shown that an ultrashort-pulse visible (420 ± 5 nm) laser is effective even against tough-to-kill, antibiotic-resistant bacteria and bacterial spores.
Their findings, published in the Journal of Biophotonics, demonstrate the utility of the laser against two bacteria from distant branches of the bacterial kingdom: Staphylococcus aureus (MRSA); and extended spectrum beta-lactamase-producing Escherichia coli (E coli). Both of these bacteria are highly resistant to chemical and physical treatments. In addition, the researchers investigated spores from the bacterium Bacillus cereus, which can cause food poisoning and is capable of withstanding boiling.
Exposure to the laser resulted in 99.9% of bacteria becoming inactivated in all cases, highlighting the impressive efficacy of the treatment.
“We previously published a paper in which we showed that the laser power matters,” explains first author Shaw-Wei (David) Tsen, from Washington University’s Mallinckrodt Institute of Radiology. “At a certain laser power, we’re inactivating viruses. As you increase the power, you start inactivating bacteria. But it takes even higher power than that, and we’re talking orders of magnitude, to start killing human cells. So there is a therapeutic window where we can tune the laser parameters such that we can kill pathogens without affecting the human cells.”
While the wavelength of the laser used in the present study corresponds to violet light, Tsen notes that the technique would be effective in other regions, including near infrared.
How does it work?
The proposed mechanism of action responsible for the laser’s success is that it forces the densely packed proteins within the bacteria to mechanically vibrate until some of their molecular bonds are dislodged. When the broken ends quickly reattach, it is often not to where they had been attached to before. The result is that regular protein function grinds to a halt and the organism dies.
The study results support the use of such lasers as a replacement for conventional antibiotic treatments in specific scenarios. “Imagine if, prior to closing a surgical wound, we could scan a laser beam across the site and further reduce the chances of infection. I can see this technology being used soon to disinfect biological products in vitro, and even to treat bloodstream infections in the future by putting patients on dialysis and passing the blood through a laser treatment device,” says Tsen.
In addition to preventing and treating bacterial infection in vivo, the laser could be used to aid in sterilizing blood prior to transfusion. “Anything derived from human or animal sources could be contaminated with pathogens,” Tsen says. “We screen all blood products before transfusing them to patients. The problem is that we have to know what we’re screening for. If a new blood-borne virus emerges, like HIV did in the 1970s and 1980s, it could get into the blood supply before we know it. Ultrashort-pulse lasers could be a way to make sure that our blood supply is clear of pathogens both known and unknown.”
The promising results of this study suggest the possible future role of ultrashort-pulse laser treatment in alleviating the healthcare burden posed by antibiotic resistance.