Gram-negative bacteria such as E. coli and other human pathogens including Pseudomonas aeruginosa, Chlamydia trachomatis, and Yersinia pestis produce a protective outer barrier comprised of a thick forest of long LPS molecules that protects them from attacks from the immune system and harmful molecules such as antibiotics. This protective LPS barrier creates a particular medical challenge as it limits the entry of antibiotics and often results in a toxic reaction when interacting with the immune system.

In the study entitled Structure of a full-length bacterial polysaccharide co-polymerase, using cryo-electron microscopy (cryo-EM) researchers were able to visualize atomic details of a fully intact component of the lipopolysaccharide biosynthesis complex. This beautiful new structure contains 8 identical copies of a protein that come together to form a large bell-shaped structure and reveals many features that have not been seen previously, bringing us a step closer to understanding the molecular mechanism of how bacterial LPS molecules are synthesized. Importantly, this new information could be exploited in the development of new antibiotics targeting Gram-negative bacteria.

One such feature, unique to this family of proteins is a proline-rich region that creates a distinctive kink in each subunit allowing the correct formation and stabilization of the complete bell-shaped complex. Developing molecules targeting this region could prevent the formation of this complex and the biosynthesis of the long, protective LPS molecules allowing a potential tidal wave of entering antibiotics that would overwhelm bacterial defences.


Read the full article here:

Structure of a full-length bacterial polysaccharide co-polymerase

Benjamin Wiseman, Ram Gopal Nitharwal, Göran Widmalm, and Martin Högbom

Nature Communications 12, 369 (2021)

DOI: 10.1038/s41467-020-20579-1