The article “Epigenomic characterization of Clostridioides difficile finds a conserved DNA methyltransferase that mediates sporulation and pathogenesis” by the Técnico alumnus Pedro Oliveira, was recently published in Nature Microbiology.
“Clostridioides (formerly Clostridium) difficile is a leading cause of healthcare-associated infections”, explains Pedro Oliveira. In the United States, this bacteria is responsible for approximately half a million infections and 30,000 deaths per year, costing the health care system about $ 5 billion a year. Pedro Oliveira and his research group focus on the epigenome of C. difficile. “This epigenome is normally composed of a group of proteins called DNA methyltransferase (DNA MTase)”, stresses the Técnico alumnus.
Following this study, which is now gaining prominence in Nature Microbiology, the team found that “by inhibiting one of these MTases, the C. difficile bacteria loses much of its ability to form spores, thus becoming much more confined”, shares Pedro Oliveira. “What’s even more exciting is that we find these MTases in almost every bacteria we know today”, says the researcher.
The work led by Pedro Oliveira is the first epigenetic study done on a large number of clinical isolates, “which allows us to draw conclusions in much more detail”, he points out. “The strategy we propose in this article can be seen as a promising plan B to combat bacterial infections”, adds Pedro Oliveira.
The opportunity to work in this area came when the Técnico alumnus worked as a postdoctoral fellow at the Institut Pasteur, in Paris. At the time, Pedro Oliveira was working on what we call regulators of the flow of genetic information in bacteria, that is, genetic systems that regulate the entry of new DNA into a cell. “These regulators operate at the epigenetic level, that is, they use small modifications in DNA to distinguish the DNA from the cell and from outside the cell”, he explains. Then, Pedro Oliveira worked at Icahn Mount Sinai School of Medicine. “At the time they had acquired a number of state-of-the-art DNA sequencers that allowed to automatically obtain information about these modifications with great precision”, says Pedro Oliveira. “At the same time, they had access to different clinical isolates of various bacteria. I proposed a line of research based on this new technology and some clinical isolates, they accepted and things turned out well”, he adds.
“The opportunity to interact with scientists who have very diverse backgrounds – such as cell biologists, computational biologists, physicists or engineers – and in the end, turning this effort into something that will benefit society”, is what motivates Pedro Oliveira.