Antibiotic resistance presents a considerable danger to global health, with forecasts indicating it could result in 10 million fatalities each year by 2050. The excessive and improper application of antibiotics, especially β-lactam antibiotics like penicillins, has fueled the emergence of resistant bacteria. These antibiotics function by obstructing bacterial cell wall synthesis, yet bacteria have evolved mechanisms such as β-lactamase enzymes to counteract them.
A team of researchers from East China University of Science and Technology in Shanghai, led by chemical biologist Hexin Xie, has developed a creative strategy to address antibiotic-resistant bacteria. They engineered a molecule that specifically targets those that express β-lactamase enzymes. This molecule comprises a β-lactamase recognition section, an iodine near-infrared photosensitizer, and hydrophilic substituents.
Typically, the molecule remains inactive as it cannot penetrate bacterial cell walls. However, when it encounters bacteria producing β-lactamase, it transforms. The enzyme cleaves the hydrophilic groups, rendering the molecule lipophilic and capable of entering the bacteria. Once inside and exposed to infrared light, the molecule turns photoactive, generating reactive oxygen species that make the bacteria more sensitive to light.
This method proved to be more effective than vancomycin, the last-resort antibiotic for gram-positive bacteria such as MRSA, both in vitro and in vivo for sterilizing MRSA-infected wounds. The technique also demonstrated potential against the gram-negative bacterium Enterobacter cloacae, albeit to a lesser extent, likely due to the more intricate cell walls of gram-negative bacteria.
The researchers are concentrating on addressing the difficulties posed by gram-negative bacteria, which often show β-lactamase resistance. Their study utilizes the bacteria’s own defense mechanisms, turning them against the pathogens. The ability to adapt this method to other enzymes that are upregulated in resistant bacteria offers a promising path for further investigation, especially for gram-negative strains.
This strategy emphasizes the promise of utilizing targeted photodynamic therapy as an innovative method to combat antibiotic resistance, providing new optimism in the battle against superbugs.