ENGINEERINGNET.BE – Biologists categorize bacteria into two major groups: Gram-positive bacteria, characterized by a single membrane, and Gram-negative bacteria, characterized by an inner and outer membrane.
It is that second membrane that makes treating Gram-negative bacteria extra difficult. The outer membrane forms an essential protective layer that shields cells from environmental stresses such as antimicrobial peptides and antibiotics.
The World Health Organization (WHO) has drawn up a top 10 list of the pathogens of most concern. Not surprisingly, that list is populated primarily by Gram-negative bacteria.
Scientists have been looking for weak spots in those double-walled bacteria for some time. A team of Belgian researchers at the VIB-VUB Center for Structural Biology has now made a breakthrough.
Although the outer membrane provides a protective shield for the bacteria, it is not infallible. Under attack from external stressors such as antimicrobial peptides, the phospholipids in the outer membrane clump together like oil slicks on the surface of the bacteria.
Such weakened areas are at risk of bursting under the water pressure in the cells, resulting in leakage of cell contents and subsequent death of bacteria. That process is called lysis in scientific jargon.
This is where SlyB comes onto the scene, a protein with a previously unknown function. When cells sense the membrane-weakening stress, SlyB springs into action.
The protein moves to the leaking phospholipids and forms ring-shaped nanodisc structures similar to a lifebuoy. The SlyB nanodiscs coat the proteins in the affected areas of the outer membrane.
This SlyB activity protects the proteins and strengthens the weaker zones of the outer membrane, preventing excessive loss of essential proteins and ensuring the survival of the bacteria. Without SlyB, the membrane weakens and the bacteria die through lysis.
“With our discovery we have gained deep insight into how Gram-negative bacteria protect themselves against conditions that destabilize the membrane,” says Arne Janssens, PhD student at VIB-VUB Center for Structural Biology.
The study not only leads to fundamental insights into a new family of nanodisc-forming proteins, but also provides innovative tools to combat the bacteria. The researchers are already taking the next steps in their research to use the unique properties of SlyB to our advantage.
The bacterial membrane proteins in the nanodiscs are purified and used in vaccines to stimulate the immune system. This way the body can better recognize incoming threats.
The discovery also offers perspectives for the development of new medicines that prevent Gram-negative bacteria from forming the nanodisc, making them no longer able to defend themselves.
2023-12-14 15:32:20
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