Exploiting a crack in the bacteria’s armor could lead to new drug therapies.

Scientists have identified a key process in how bacteria protect themselves from attack, and heralds a new strategy in the search for antibiotics.

Researchers at the University of Leeds have reconstructed how bacteria build their outer, defensive wall, in essence, the cell’s armor.

Research has focused on gram-negative bacteria. Escherichia coliBut the process they discovered is shared by many pathogenic gram-negative bacteria, so it could be important in addressing other gram-negative pathogens, including the top three on the World Health Organization list of priority pathogens.

The findings are published today in the journal. Nature’s Communications.

Dr. Antonio Calabrese, an academic member of the University at the Astbury Center for Structural Molecular Biology, led the research. He said: “Our findings are changing the way we think about how these cells constantly renew and replenish the proteins that make up the outer membrane.

“Understanding that process of how bacteria build their cell walls in greater detail can identify ways in which we could intervene and disrupt it.

“By doing so, we can either destroy bacteria entirely or slow down the rate at which they divide and grow, making bacterial infections less severe.

“We are at the beginning of a search that could result in new drug-based therapies that work alone or with existing antibiotics to attack these disease-causing bacteria.”

Research has focused on the role of a protein called SurA. Known as a chaperone, SurA’s job is to martialize other proteins from where they are made, in the center of the cell, to where they are needed, in this case to reinforce the outer wall of the bacterium.

Proteins are long chains of amino acids that must take a defined structural shape to function effectively. Without the SurA chaperone, the essential proteins necessary to build the cell wall are at risk of losing their structural integrity on their journey to the outer membrane.

Using advanced analytical techniques, the scientists mapped how the SurA chaperone recognizes proteins to transport them to the bacterial outer membrane.

Dr. Calabrese said: “For the first time we have been able to see the mechanism by which the chaperone, SurA, helps transport proteins to the bacterial outer membrane. In effect, it does so by cradling the proteins, to ensure their safe passage. Without SurA , the delivery pipe is broken and the wall cannot be built properly. “

Professor Sheena Radford, FRS, director of the Astbury Center for Structural Molecular Biology, said: “This is an exciting discovery in our quest to find weak spots in the arsenal of a bacterium that we can attack to stop bacterial growth in its tracks and build new and much-needed antibiotics

“It’s the first days, but now we know how SurA works and how it binds to its protein clients. The next step will be to develop molecules that interrupt this process, which can be used to destroy pathogenic bacteria.”

Dr. David Brockwell, associate professor at the Astbury Center for Structural Molecular Biology, said: “It was only through the work of a large team from across the Astbury Center that we were finally able to understand how SurA transports proteins to the outer membrane bacterial. ”