Wednesday, 23 November 2016

Showing how bacteria make biofilms cell-by-cell

Princeton researchers have shown the mechanics of how bacteria build up slimy masses (biofilms), cell by cell. When encased in biofilms in the human body, bacteria are a thousand times less susceptible to antibiotics, making certain infections, such as pneumonia, difficult to treat.

The researchers chose Vibrio cholerae for their model biofilm organism because of its long history of study and threat to human health, causing the diarrheal disease cholera. A curved, rod-shaped bacterium, V. cholerae lives as a free-swimming cell in brackish water or saltwater. When V. cholerae makes contact with a food particle, perhaps on the shell of a crab or a shrimp, or a human intestinal cell during disease, the bacterium attaches itself and begins to reproduce. The expanding colony's members secrete a glue-like substance to keep from getting washed away and to protect themselves from competing bacteria.

At first, the bacterial colony expanded horizontally on the given surface in the experiment. As each cell split, the resulting daughter cells firmly attached to the surface alongside their parent cells. Squeezed by increasing numbers of offspring bacteria, however, the cells at the heart of expanding colony were forced to detach from the surface and point vertically. The bacterial colony thus went from a flat, two-dimensional mass to an expanding, three-dimensional blob, all held together by gunk in the developing biofilm.
The Princeton team looked deeper into the genetics behind this cellular behavior. A single gene, dubbed RbmA, is key to behavior in which new cells connect in such a way to develop a three-dimensional biofilm. When the researchers deactivated the gene, a big, diffuse and floppy biofilm formed. When RbmA performed as normal, though, a denser, stronger biofilm resulted as the cells stayed linked to each other. Thus, RbmA provides the biofilm its resilience, providing insight into a potential Achilles heel that could be targeted for therapeutic intervention.
Ongoing work is now measuring the physical forces experienced by cells uplifting at the biofilm's center so the overall mechanics can be precisely worked out.
For further details, see:
Jing Yan, Andrew G. Sharo, Howard A. Stone, Ned S. Wingreen, Bonnie L. Bassler. Vibrio choleraebiofilm growth program and architecture revealed by single-cell live imaging. Proceedings of the National Academy of Sciences, 2016; 113 (36): E5337 DOI: 10.1073/pnas.1611494113

Posted by Dr. Tim Sandle