“You could say that we are adding a piece of the puzzle to the understanding of how antibiotic resistance spreads between bacteria.”
-Prof Ronnie Berntsson, Associate Professor, Umeà University, Sweden.
The bacterium of interest in this study is Enterococcus faecalis, a common cause of hospital infections, to provide clues to our understanding as to how the antibiotic resistance spreads. The enzyme that breaks down the bacterial outer protective layer which is the cell wall and then facilitates the transfer of genes for antibiotic resistance is demonstrated in this study. The antibiotics no longer work effectively for treatment against this bacterium due to resistance. This bacterium can also have resistance via the type 4 secretion systems, T4SS. The protein complex involved here acts as some kind of copying device, enabling the property of genetic material to be spread to other forms of bacteria. Resistance against antibiotics is possibly moved between bacteria with the T4SS involvement.
The T4SS is the enzyme PrgK, that has the ability to break down bacterial cell wall and facilitates the transfer of properties between bacteria. The enzyme has three domains: LytM, SLT, and CHAP. Prg functions as scissors to cut the bacterial cell wall. Contrary to what researchers have thought, it was just the SLT domain that was active but in a different way. The other two domains play out the crucial role of enzyme regulation. The researchers have identified another T4SS protein, the PrgL that binds to PrgK, ensuring that it (PrgK) is in the right place. “The findings are important for continued research into how to prevent T4SS from transferring properties such as resistance to antibiotics to other bacteria,” explains Josy ter Beek, a Staff Scientist at Umeà University.
The conducting of the study took place through combining biochemical analyses of the protein that were linked to the functional studies in vivo, and were later supplemented with structural studies of the PrgK by utilising both X-ray crystallography and AlphaFold modelling.
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