Scientists disable protein folding to weaken antibiotic resistant bacteria

Wednesday 22 April 2026 - 07:50

By: Dakir Madiha

Scientists disable protein folding to weaken antibiotic resistant bacteria

Researchers have identified a critical weakness in drug resistant bacteria by disrupting the protein folding processes required for their survival, a breakthrough that could restore the effectiveness of existing antibiotics. The findings focus on disabling the mechanisms bacteria use to build resistance enzymes, removing both their defenses and their ability to shield neighboring microbes.

The study examined two pathogens commonly found together in lung infections linked to cystic fibrosis: Pseudomonas aeruginosa and Stenotrophomonas maltophilia. The latter is known for its resistance to nearly all available antibiotics and relies on enzymes called beta lactamases to neutralize treatments such as penicillins and cephalosporins. These enzymes not only protect the producing bacteria but also break down antibiotics in the surrounding environment, indirectly protecting nearby susceptible bacteria. This cross protection has been shown to accelerate the emergence of new resistant strains, worsening clinical outcomes.

Scientists targeted the oxidative protein folding system, a cellular pathway bacteria depend on to correctly form resistance enzymes. By combining genetic deletions with chemical inhibitors, the team disrupted this folding process, rendering multiple resistance mechanisms inactive. As a result, both bacterial species became significantly more sensitive to standard antibiotics, demonstrating the central role of protein folding in maintaining resistance.

Experiments conducted on infected wax moth larvae, a widely used model for studying bacterial infections, showed that pairing protein folding inhibitors with conventional antibiotics improved survival rates. The intervention also eliminated the ability of Stenotrophomonas maltophilia to protect coexisting Pseudomonas aeruginosa, effectively breaking the cooperative defense that often complicates treatment in mixed infections.

Researchers say the implications extend beyond cystic fibrosis cases. The oxidative protein folding system exists only in bacteria and is conserved across many species, making it a promising universal target. By focusing on this shared vulnerability, scientists aim to develop a new class of adjunct therapies that enhance the performance of existing antibiotics rather than replacing them, offering a practical strategy against rising antimicrobial resistance.