WASHINGTON: Scientists have identified how bacteria produce a protein that allows the disease-causing pathogens to stick to human cells, a finding that may lead to the development of novel antibiotics.
All bacteria have a standard secretion system that allows them to export different types of proteins outside of their cells.
An important class of extracellular molecules produced by pathogenic bacteria are adhesins, proteins that enable bacteria to adhere to host cells.
For unknown reasons, the SRR (serine-rich-repeat) adhesins of Staphylococcus and Streptococcus bacteria – pathogens that can be involved in serious infections such as bacterial meningitis, bacterial pneumonia and pericarditis – are transported through a secretion pathway that is similar to the standard system, but dedicated solely to adhesin.
It would be as if a warehouse that processes many types of goods were to have a separate set of doors and forklifts for just one of its wares.
Who oversaw the new study, wanted to understand what exactly these dedicated molecular supply chains were doing.
“I was intrigued by the fact that there is a second secretion system in some bacteria that is separate from the canonical secretion system and is just dedicated to the secretion of one protein,” said Tom Rapoport, a professor at Harvard Medical School in the US.
“There is a whole machinery, and it’s only doing one thing,” Rapoport said.
Yu Chen, a postdoctoral research associate who led the investigation, found that, in order to be transported, the adhesin protein needed to be modified with specific sugars by three enzymes acting in a specific sequence.
These sugar modifications stabilize the protein and enhance its stickiness to target cells.
Furthermore, the experiments showed that two proteins in the adhesin-specific pathway, whose function had previously been mysterious, seemed to be able to bind to these sugars, presumably enabling them to carry the adhesin to the cell membrane where adhesin’s dedicated exit channel is located.
The reason that these bacteria use this separate export pathway for adhesins remains elusive.
However, because this pathway is unique to strep and staph bacteria, the new understanding of its components could help researchers develop highly targeted antibiotics to treat infections caused by these bacteria in the future.
“You could imagine that you could develop novel antibiotics that could target this pathway. They would be very specific for pathogenic bacteria,” Rapoport said. (AGENCIES)
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