Study reveals new mechanism for protecting bacterial cell walls

Researchers from Umeå University in Sweden and Cornell University in the United States have discovered a widespread mechanism in bacteria that strengthens their defenses against environmental threats.

This discovery, which could be important for research aimed at developing new treatments, shows how a specific cross-linking mode in the peptidoglycan cell wall inhibits the activity of certain cell wall-degrading enzymes and thus protects bacteria.

Bacteria are protected by the peptidoglycan cell wall, which helps them resist internal turgor pressure and external damage, such as attacks from other bacteria and viruses. To grow and stay strong, bacteria need a balance of enzymes that build and break down the cell wall.

Lytic transglycolases are an important type of enzymes that break down peptidoglycan chains. However, the regulatory mechanisms governing them remain unclear so far.

The study, conducted by Felipe Cava’s lab at Umeå University in collaboration with colleagues at Cornell University in New York, and published in Nature Communicationsreveals that a specific type of crosslinking in the cell wall, known as LD crosslinking, inhibits the activity of lytic transglycolases.

This has major biological consequences. For example, some bacteria use this type of enzyme to release cell wall fragments that modulate the host’s immune system. Some bacteria and viruses also use this type of enzyme to kill other bacteria. By controlling the activity of these enzymes, bacteria can potentially protect themselves from the immune system and attacks by other bacteria and viruses.

“This discovery fills an important gap in understanding the role of LD cross-linking in cell wall homeostasis,” Cava says. “We have shown that bacteria can enhance their protection against environmental threats, including phage attack, through a single structural modification of their cell wall.”

This discovery provides new insights into bacterial cell wall homeostasis and opens potential avenues for the development of novel antibacterial therapies.

“By targeting LD cross-linking, new treatments could be designed to weaken the bacteria’s defenses, making them more vulnerable to antibiotics and immune responses,” says Laura Alvarez, a researcher at the Department of Molecular Biology at Umeå University and first author of the study.