A new study sheds light on the mechanism behind the spread of antibiotic resistance. The research reveals how an enzyme breaks down the protective outer layer of bacteria, known as the cell wall, to facilitate the transfer of resistance genes.
“This study adds a piece to the puzzle of how antibiotic resistance moves between bacteria,” explains Ronnie Berntsson, an Associate Professor at UmeĆ„ University who co-authored the study.
The researchers at UmeƄ University focused on Enterococcus faecalis, a bacterium commonly associated with hospital-acquired infections. These bacteria have developed resistance to antibiotics, making treatment challenging. They can transfer this resistance using type 4 secretion systems (T4SS), which are protein complexes that act as conduits for spreading genetic material, including antibiotic resistance traits, to other bacteria.
A crucial component of T4SS is the enzyme PrgK, which breaks down the bacterial cell wall to facilitate the transfer of traits between bacteria. PrgK comprises three domains – LytM, SLT, and CHAP.
PrgK functions like scissors, cutting through the bacterial cell wall. Contrary to the researchers’ initial assumptions, they discovered that only the SLT domain is active, albeit in a different manner. The other two domains play a key role in regulating the enzyme. Additionally, the researchers found that another T4SS protein, PrgL, binds to PrgK, guiding it to the correct location within the protein complex.
“These findings are crucial for future research aiming to prevent T4SS from transferring traits like antibiotic resistance to other bacteria,” notes Josy ter Beek, a Staff scientist at UmeĆ„ University.
The study involved a combination of biochemical analyses of the protein, in vivo functional studies, and structural examinations of PrgK using X-ray crystallography and AlphaFold modelling techniques.
