Photodynamic Method Boosts Antibiotics Against Drug-Resistant Bacteria

Multidrug-resistant bacteria are considered a serious threat to infection control. Faced with the increasing difficulty of developing new antibiotics to combat resilient bacterial strains, scientists are turning to photodynamic inactivation (PDI), a light-based approach to breaking antimicrobial resistance.

PDI strengthens the effect of antibiotics and induces oxidative stress in microorganisms through the interaction of light with a photosensitizer. The photosensitizer is energized in PDI by absorbing visible light to form reactive oxygen species that trigger bacterial inactivation by oxidizing and destroying microorganisms or weakening their resistance to antibiotics.

A research group at the University of São Paulo’s Optics and Photonics Research Center analyzed patient samples containing Staphylococcus aureus, a bacterium that causes a range of diseases, from skin infections to pneumonia. Courtesy of Janice Haney Carr/CDC PHIL.

In recent work, researchers at the University of São Paulo’s Optics and Photonics Research Center showed that PDI can modify bacterial sensitivity to antibiotics and reduce the resistance and persistence of both standard and clinical strains. The researchers, led by professor Vanderlei Salvador Bagnato, investigated the effects of photodynamic action on resistant bacteria collected from patients and bacterial cells with laboratory-induced resistance. They focused their investigation on Staphylococcus aureus, a bacterium that causes a range of diseases, from skin infections to pneumonia.

The researchers used 10 μM, 10 J/cm² of the photosensitizer curcumin at 450 nm with antibiotics. Curcumin has been shown to strengthen some antibiotics by affecting the bacterial membrane and other cellular components. Three antibiotics — amoxicillin, erythromycin, and gentamicin — were treated with curcumin.

The results showed that five cycles of PDI were sufficient to break bacterial resistance. The researchers found that S. aureus was most susceptible to gentamicin, although the other two antibiotics also proved effective against the bacteria after treatment with PDI.

In addition, the researchers concluded that a reduction in the degree of antimicrobial resistance through photo-oxidative action can mitigate antibiotic failures. Photodynamic action not only improves infection control, but also modifies the degree to which antimicrobials are susceptible to bacteria by decreasing bacterial resistance to below breakpoints and controlling the biofilm formation, which is an important bacterial virulence factor.

“We discovered that PDI doesn’t always destroy the bacteria, but it does destroy part of the mechanisms they use to become drug-resistant,” Bagnato said. “This led to the idea of trying an oxidative shock to make them susceptible to antibiotics.”

Historically, the primary strategy in the fight against multidrug-resistant bacteria infections has been the development of new antimicrobial drugs. However, failures in antibiotic treatments occur. Antibiotics act on a certain bacterial cell compartment, depending on their type, while PDI acts in the entire bacterial cell, causing multiple damages.

The researchers said that an increase or a complete recovery of a bacterium’s susceptibility to antibiotics could be a way to prolong the useful life of recent classes of antibiotics, which is essential to avoid infection control collapses. They said that a broader assessment of other antibiotics, microorganisms, and photosensitizers is needed to achieve a full understanding of the mechanisms of action and interaction between PDI and antibiotics.

The research was published in the Proceedings of the National Academy of Sciences (www.pnas.org/doi/10.1073/pnas.2311667120).