Sharpest ever images of live bacteria unravel the secrets of superbugs
By using a nanoscale needle tip to probe the intricate exterior structures of Escherichia coli, scientists have produced the sharpest images ever of living bacteria. With this new perspective of its patchy protective layer, the researchers hope to further their understanding of the way bacteria can rapidly grow, and reveal chinks in their armor that may help us tackle the serious problem of antibiotic resistance.
This unprecedented view of the tough outer membrane of Gram-negative bacteria, a group that includes species such as A. baumannii, P. aeruginosa, Salmonella and E. coli, comes from scientists at University College London working to better understand their key defense against today's medical treatments. The outer membrane of Gram-negative bacteria is increasingly effective at repelling antibiotics, and these types of superbugs could kill millions per year by 2050, experts have warned.
"The outer membrane is a formidable barrier against antibiotics and is an important factor in making infectious bacteria resistant to medical treatment. However, it remains relatively unclear how this barrier is put together, which is why we chose to study it in such detail," explains corresponding author Professor Bart Hoogenboom.
To do this, the team combed the exterior of E. Coli with a tiny needle bearing a tip just a few nanometers wide. This enabled them to detect and in turn image the very fine molecular structures on the surface of the bacteria, and show how the outer membrane features microscopic holes formed by proteins that allow the passage of nutrients while preventing toxins from entering.
To the researchers' surprise, some patches of the membrane appeared to contain no proteins at all, instead bearing molecules with sugary chains known as glycolipids, and parts of the membrane had actually flipped inside out as a result of mutations. These defects correlated with a higher sensitivity to an antibiotic called bacitracin, which is usually only effective against Gram-positive bacteria.
"The textbook picture of the bacterial outer membrane shows proteins distributed over the membrane in a disordered manner, well-mixed with other building blocks of the membrane," explains study author Georgina Benn. "Our images demonstrate that that is not the case, but that lipid patches are segregated from protein-rich networks just like oil separating from water, in some cases forming chinks in the armor of the bacteria. This new way of looking at the outer membrane means that we can now start exploring if and how such order matters for membrane function, integrity and resistance to antibiotics."
In addition to revealing potential weak spots that can be targeted with antibiotics, the work may also reveal how bacteria can grow rapidly while maintaining a densely packed outer membrane. The researchers suspect that the glycolipid patches could be more malleable than the protein ones, allowing the membrane to stretch and adapt as the bacterium grows.
The research was published in the journal Proceedings of the National Academy of Sciences.