Antibiotic-resistant bacteria are poised to become one of the most urgent global health issues in the next few decades, if we don't do anything about it. Now researchers at the University of Montreal (UdeM) may have created a new weapon in the war, by preventing bacteria from transferring genes to each other that help them develop resistance to antibiotics.
Recent reports have warned that these so-called superbugs could be responsible for 10 million deaths a year by 2050, and alarmingly, our last line of defense has already begun to fail. To prevent that apocalyptic scenario, we need techniques and drugs that fight the war on a wide range of fronts, and scientists have sprung into action by developing new tests, molecules, materials and lighting systems, as well as extracting natural remedies from honey, maple syrup, berries and breast milk.
The UdeM team focused on blocking plasmids, fragments of DNA that microbes use to transfer useful genes to one another. Antibiotic resistance is often spread between bacteria through this process, so cutting off their transmission could be a handy weapon in the war against superbugs.
First, the researchers scanned through a library of small chemical molecules, searching for those that bind to a protein called TraE, which is a crucial component of the process. Once they'd identified the candidates, the team used X-ray crystallography to pinpoint exactly where those molecules bind on the TraE protein, so they could then develop molecules that home in on that spot more effectively.
"You want to be able to find the 'soft spot' on a protein, and target it and poke it so that the protein cannot function," says Christian Baron, co-author of the study. "Other plasmids have similar proteins, some have different proteins, but I think the value of our study on TraE is that by knowing the molecular structure of these proteins we can devise methods to inhibit their function."
Using that knowledge, the researchers designed stronger binding molecules, and managed to reduce the transfer of antibiotic resistance genes. Next, the researchers want to find more of these inhibitor molecules, as well as adapt the technique to fight other disease-causing bacteria.
"The beauty of what we are working on here is that the proteins are very similar to proteins that bacteria use to cause disease," says Baron. "So from what we learned about the TraE protein and about finding its 'soft spot,' we can actually apply this approach to other bacteria that cause diseases. One of those is Helicobacter pylori, which is a gastric pathogen that causes ulcers and stomach cancers. We're working on that one specifically now, but there are many others."
The research was published in the journal Scientific Reports.
Source: University of Montreal