Overcoming inhibition: How bacteria build safe havens

To build biofilms — the slimy plaques bacteria create to better cling to surfaces, cause disease and resist antibiotics — they must first release a built-in brake.

Researchers at the University of Virginia School of Medicine have discovered how the breaking of a molecular interaction plays a vital role in the creation of biofilms, a finding that could allow scientists to devise better ways to destroy these bacterial boarding houses. That’s a matter of grave importance, as biofilms allow bacteria to thrive where they shouldn’t, in places such as hospitals, restaurants and even your shower.

The UVA researchers have unraveled a key process within bacteria that culminates in the production of cellulose, an important building block of both biofilms and plant cell walls. Specifically, the researchers showed how a signaling molecule overcomes an auto-inhibited state of the enzyme that is responsible for cellulose production. Releasing this molecular brake mobilizes an important gating loop, thereby activating the enzyme and leading to the creation of cellulose.

The discovery could lead to the development of new drugs to battle bacteria. “By showing how this signaling molecule activates the production of cellulose, hopefully we can come up with ways to interfere with this signaling mechanism to prevent biofilm formation,” said researcher Jochen Zimmer, DPhil, of the UVA Department of Molecular Physiology and Biological Physics.

“Our body doesn’t utilize this signaling mechanism,” noted researcher Jacob Morgan, a graduate student in Zimmer’s lab. “So if we can design drugs to selectively block the signal, we can attack bacterial infections and reduce the risk of side effects on the human body.”

In addition to preventing disease, scientists could use the new mechanistic insights to engineer new and better biomaterials for industrial purposes, such as biofuels. “It’s a window into how the world’s most abundant macromolecule is synthesized,” said researcher Josh McNamara.

The researchers reveal how the signal activates bacterial cellulose production in a new paper published by Nature Structural & Molecular Biology. The paper was authored by Morgan, McNamara and Zimmer, all of the Center for Membrane Biology in the Department of Molecular Physiology and Biological Physics.

The work was done in collaboration with the Argonne National Laboratory in Argonne, IL.