A new approach to combating antibiotic resistance could help prevent disease by making bacteria vulnerable to treatment again.
Researchers, including experts from Imperial College London, have found a way to weaken antibiotic-resistant bacteria that cause human disease, such as E. coli, K. pneumoniae and P. aeruginosa. This can be done by inhibiting a protein that forms antibiotic resistance inside the bacterium.
Dr. Despoina Mavridou, assistant professor of molecular biology at the University of Texas at Austin, who led the research team, said this is an entirely new way to fight resistance, a major challenge for scientists.
The study found that antimicrobial resistance was directly responsible for at least 1.27 million deaths worldwide in 2019. In addition, scientists have fears that bacteria are becoming increasingly resistant to existing antibiotics. Because of this, researchers are struggling to find new alternative medicines.
Antibiotic-resistant bacteria contain many different proteins that neutralize antibiotics. In order to neutralize an antibiotic, the resistance proteins within the bacterium must be folded into the correct shape. Dr. Mavridou’s research team found that the DsbA protein is responsible.
As a result of their pilot study, published in the journal eLife, the researchers inhibited DsbA to prevent the formation of resistant proteins using chemicals that cannot be applied directly to patients.
The team plans to work on developing inhibitors that can be safely applied to humans without losing their protective effect.
Dr Chris Furniss, one of the lead authors of the study at Imperial College London’s Department of Life Sciences, said that discovering new antibiotics is a difficult but crucial task that will help extend the life of existing antimicrobials.
“Our results show that by influencing the formation of disulfide bonds and protein folding, antibiotic resistance in several major pathogens and resistance mechanisms can be reversed.
This means that future development of clinically useful DsbA inhibitors could provide the basis for new treatments for resistant infections using currently available antibiotics.”
The researchers hope to eventually combine the DsbA inhibitor with existing antibiotics to restore the drugs’ ability to kill bacteria.
Previously, scientists have known that DsbA is involved in a number of pathogen functions, such as creating toxins to attack host cells and helping to assemble needle-like systems that can deliver these toxins to human cells and cause disease.
Nicole Kaderabkova, a former graduate student at Imperial College and now a postdoctoral researcher at UT Austin and co-lead author of the study, said: “We concluded that if DsbA is required to fold resistance proteins, preventing it from working would indirectly suppress their function.”