NEWS Even highly antibiotic-resistant bacteria become more vulnerable when their cell wall transport system is disrupted, according to a new study from Umeå University. The discovery reveals a previously overlooked weakness that could help researchers develop new strategies to combat antibiotic resistance.
SSMF-funded postdoctoral researcher Gabriel Torrens and Professor Felipe Cava have shown that resistant bacteria depend on the lipid molecule undecaprenyl phosphate to transport building blocks needed to construct the cell wall. Disrupting this transport significantly weakened the bacteria's resistance.
ImageMattias PetterssonThe search for new antibiotics remains crucial, but we also need smarter ways to extend the lifespan of the antibiotics we already have.
“The search for new antibiotics remains crucial, but we also need smarter ways to extend the lifespan of the antibiotics we already have. We wanted to find out whether resistant bacteria could be pushed into an evolutionary dead end, where the very mechanisms that help them survive instead make them vulnerable to existing antibiotics,” says Felipe Cava, Professor at the Department of Molecular Biology at Umeå University.
Antibiotic resistance is a growing global health challenge. As bacteria evolve resistance to medicines, infections become increasingly difficult to treat, raising the risk of severe illness and death. Now, researchers at Umeå University have identified an unexpected vulnerability in certain resistant bacteria that could potentially be exploited to make them susceptible to antibiotics once again.
The study, published in Nature Communications, was led by Felipe Cava's research group at Umeå University in collaboration with researchers from the Spanish National Research Council (CSIC) and Umeå University Hospital.
Felipe Cava is Professor of Molecular Biology at Umeå University. His research focuses on uncovering new insights into one of the most remarkable bacterial structures: the cell wall.
ImageMattias Pettersson, simon ohman jonsson inhousebyranBacteria are protected by a robust cell wall that helps them survive in harsh environments. The cell wall is also the target of β-lactam antibiotics, a class of drugs that includes penicillins and remains among the most widely used treatments for bacterial infections. Some bacteria, however, have evolved the ability to continue building their cell wall despite antibiotic treatment, making them resistant.
A well-known example is methicillin-resistant Staphylococcus aureus (MRSA), which causes difficult-to-treat infections worldwide. Over time, these bacteria can acquire additional mutations that further strengthen their resistance.
The researchers found that resistant bacteria depend on a small lipid molecule called undecaprenyl phosphate, which acts as a conveyor belt for the building blocks needed to construct the cell wall. When this transport system was disrupted, it became considerably more difficult for the bacteria to maintain their resistance.
In the study, the researchers tracked how MRSA evolved during antibiotic treatment. They identified genetic changes that enabled the bacteria to regain resistance. However, when the transport of cell wall building blocks was disrupted, this evolutionary route was effectively blocked.
The researchers also found that bacteria carrying new resistance mutations often grew more slowly and were less capable of causing infection.
“What surprised us was that some mutations that help bacteria survive antibiotic treatment simultaneously create new vulnerabilities. Rather than becoming stronger in every respect, the bacteria appear to be forced into a trade-off,” says Gabriel Torrens, first author of the study and postoctoral fellow at the Department of Molecular Biology at Umeå University.
The phenomenon was observed not only in MRSA but also in Streptococcus pneumoniae, a bacterium that commonly causes diseases such as pneumonia. This suggests that the same vulnerability may exist across many antibiotic-resistant Gram-positive bacteria, a group that includes staphylococci and pneumococci.
The researchers believe the discovery opens a new avenue for future therapies aimed at restoring the effectiveness of existing antibiotics. Its potential to lead to new treatments has already resulted in the filing of a patent application.
The study was funded by the Swedish Research Council (research environment grant within infection and antibiotics), the Knut and Alice Wallenberg Foundation, and the Kempe Foundations. Gabriel Torrens was recruited to Umeå University through the ‘Excellence by Choice’ postdoctoral programme and is currently funded by the Swedish Society for Medical Research (SSMF).
Gabriel Torrens, Sean W Bisset, Maria López-Bravo, Anders F Johansson, Daniel Lopez, Felipe Cava: Statin-induced lipid carrier stress reveals a conserved vulnerability in β-lactam-resistant Gram-positive bacteria. Nat Commun. 2026 Jul 20;17(1):6680. doi: 10.1038/s41467-026-75729-8.
