Microscopy image of a living E. coli bacterium, exposing the irregular nature of its protective external membrane. A largely packed network of proteins is disrupted by smooth, protein-free islands (labeled by rushed lines in the inset). Credit: Benn et al.
UCL The sharpest images ever of living bacteria have been taped by UCL scientists, exposing the complex architecture of the protective layer that surrounds many bacteria and makes them more difficult to be killed by antibiotics.
The research study, published today (October 25, 2021) in Proceedings of the National Academy of Sciences of the USA and done in cooperation with scientists at National Physical Laboratory, Kings College London, University of Oxford, and Princeton University, reveals that germs with protective outer layers– called Gram-negative bacteria– may have stronger and weaker areas on their surface.
The team discovered that the protective outer membrane of the bacteria consists of thick networks of protein foundation rotated by patches that do not appear to include proteins. Instead, these spots are improved in particles with sugary chains (glycolipids) that keep the external membrane tight.
This is an important finding because the difficult outer membrane of Gram-negative germs prevents certain drugs and antibiotics from permeating the cell: this external membrane belongs to the reason antimicrobial resistance of such bacteria (including A. baumannii, P. aeruginosa, and enterobacteriaceae such as Salmonella and E. coli) is now thought about a greater risk than that of Gram-positive bacteria such as resistant S. aureus ( well understood as MRSA).
” The outer membrane is a formidable barrier against antibiotics and is an important consider making transmittable germs resistant to medical treatment. However, it stays reasonably unclear how this barrier is assembled, which is why we picked to study it in such detail,” explained matching author Professor Bart Hoogenboom (London Centre for Nanotechnology at UCL and UCL Physics & & Astronomy).
” By studying live germs from the molecular to cellular scale, we can see how membrane proteins form a network that spans the whole surface of the bacteria, leaving small gaps for patches which contain no protein. This recommends that the barrier might not be similarly tough to breach or stretch all over the germs, but may have stronger and weaker areas that can likewise be targeted by antibiotics.” To better understand this architecture, the scientists ran a tiny needle over living Escherichia coli ( E. coli) germs, hence “feeling” their total shape. Given that the idea of the needle is just a few nanometres broad, this made it possible to envision molecular structures at the bacterial surface area.
The resulting images reveal that the entire external membrane of the bacteria is stuffed with tiny holes formed by proteins that enable the entry of nutrients while avoiding the entry of toxins. The outer membrane was known to contain lots of proteins, this congested and immobile nature had been unanticipated.
These spots consist of a glycolipid normally discovered on the surface area of Gram-negative germs. In this case, the look of these flaws correlated with improved level of sensitivity to bacitracin, an antibiotic normally just reliable versus Gram-positive, however not versus Gram-negative bacteria.
As discussed by Georgina Benn, who did the microscopy on the germs in Professor Hoogenbooms laboratory at UCL: “The book image of the bacterial outer membrane shows proteins distributed over the membrane in a disordered way, well-mixed with other foundation of the membrane. Our images demonstrate that is not the case, but that lipid spots are segregated from protein-rich networks similar to oil separating from water, sometimes forming chinks in the armor of the bacteria. This new way of looking at the external membrane indicates that we can now start checking out if and how such order matters for membrane function, integrity, and resistance to prescription antibiotics.” The team likewise hypothesizes that the findings may help describe ways by which germs can keep a firmly packed, protective barrier while still allowing rapid growth: the common germs E. coli doubles in size and then divides in 20 minutes under beneficial conditions. They recommend that the glycolipid spots may enable more stretch of the membrane than the protein networks, making it much easier for the membrane to adjust to the growing size of the germs.
Reference: “Phase separation in the outer membrane of Escherichia coli” 25 October 2021, Proceedings of the National Academy of Sciences.DOI: 10.1073/ pnas.2112237118.
The work was kindly moneyed by the UKRI, the National Institutes of Health, the European Research Council, and the UK Department for Business, Energy and Industrial Strategy.
Microscopy image of a living E. coli germs, exposing the irregular nature of its protective external membrane.” By studying live bacteria from the molecular to cellular scale, we can see how membrane proteins form a network that spans the whole surface area of the bacteria, leaving small gaps for patches that consist of no protein. As explained by Georgina Benn, who did the microscopy on the germs in Professor Hoogenbooms lab at UCL: “The textbook image of the bacterial external membrane shows proteins distributed over the membrane in a disordered way, well-mixed with other structure blocks of the membrane. The team likewise hypothesizes that the findings might help explain methods by which bacteria can preserve a tightly loaded, protective barrier while still permitting fast growth: the common germs E. coli doubles in size and then divides in 20 minutes under beneficial conditions. They suggest that the glycolipid spots may permit for more stretch of the membrane than the protein networks, making it easier for the membrane to adapt to the growing size of the germs.
