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Clever chemistry turns antibiotic-resistant bacteria’s own defences against them
By Tim Wogan2026-06-26T08:21:00+01:00
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Source: © David Parker/Science Photo Library<br>Photodynamic therapy could become a tool to treat wounds infected with antibiotic resistant bacteria
Antibiotic-resistant bacteria can be selectively destroyed by a molecule that uses their our own immunity against them to make them photosensitive, researchers in China have shown. The compound was shown to be more active than vancomycin against some strains of MRSA, killing them almost completely upon exposure to light.
Antimicrobial resistance is a growing threat that could potentially cause up to 10 million deaths per year by 2050 and make many clinical procedures like surgeries too risky. β-lactam antibiotics such as penicillins have been widely used for over 80 years, presently accounting for around 65% of all prescribed antibacterial drugs. The β-lactam ring binds to bacteria, blocking the synthesis of their cell walls. Bacteria have developed resistance to these antibiotics, most commonly by synthesising β-lactamase enzymes, which hydrolyse the ring.
Chemical biologist Hexin Xie and colleagues at East China University of Science and Technology in Shanghai developed an elegant method to specifically target bacteria that express β-lactamase enzymes. They synthesised a molecule comprising a β-lactamase recognition unit, an iodine near-infrared photosensitiser and hydrophilic substituents. The complete molecule was unable to penetrate cell walls and was not photoactive.
When the molecule encountered a bacterium that expressed β-lactamase, however, the hydrophilic groups were cleaved off. This simultaneously made the molecule lipophilic – and thus able to enter the bacterium – and photoactive, producing reactive oxygen species when exposed to infrared light. The combined effect made cells expressing β-lactamase photosensitive. ‘[The molecule] can accumulate within bacteria,’ explains Xie. ‘Between bacteria and the incubation medium, the [concentration] ratio can be more than 2000-fold.’
Source: © 2026 Fangfang Chen et al<br>The bacterial enzyme that inactivates penicillins activates the new photosensitiser, letting it enter bacteria and start generating reactive oxygen species that kill them
The researchers demonstrated the molecule’s effectiveness in vitro and in vivo, showing that in MRSA with β-lactam resistance mediated by β-lactamase, photodynamic therapy could be more effective than even vancomycin – the present antibiotic of last resort for gram-positive bacteria such as Staphylococcus aureus – for sterilising MRSA-infected wounds.
It was also effective against the gram-negative bacterium Enterobacter cloacae, but less so. The researchers believe this is because gram-negative bacteria, which have more complex, multi-layered cell walls, are simply more resistant to photodynamic therapy. This is their next challenge. ‘β-lactamase is actually more common in gram-negative bacteria,’ says Xie. ‘Our study was about using β-lactamase to activate the compound and using the mechanism to have it accumulate within the [resistant] bacteria. We’re now working on use of something beyond a photosensitiser [to kill the bacteria].’
‘This idea of being able to turn the bacteria’s defence system on itself is really cool, and...