New knowledge about coliforms to counteract multi-resistance
Study initiated by the Morth Group at NCMM, and completed at DTU Bioengineering, has enabled researchers to map how coliform bacteria attach to the intestinal wall giving hope for development of new treatments.
Coliform infections can still be treated with antibiotics, but instances of multi-resistance against several types of broad-spectrum antibiotics have been noted. There is therefore an urgent need to develop alternative ways of controlling such infections. In order to be able to do so, it is a good idea to know and understand the basic structure of the bacterium.
"Specifically, this means that intitims can reach further when looking for a receptor to bind to. It is therefore probably even more effective at infecting an organism than previously thought, and this is important knowledge when it comes to developing new methods to fight coliform infections," commented Professor Jens Preben Morth, DTU Bioengineering, and former group leader at NCMM.
That is exactly what Julia Weikum, originally a PhD student at NCMM, set out to do in the study 'The extracellular juncture domains in the intimin passenger adopt a constitutively extended conformation inducing restraints to its sphere of action', which has just been published in the well-known journal Scientific Reports from Nature.
Together with fellow researchers from Scandinavia, the UK, Germany, and Japan, she is the first in the world to fully map the strand that two of the most pathogenic coliforms, EHEC and EPEC, use to infect an organism. It is a good place to start, because if you can get a complete understanding of how the bacterium infects, you can take the next step and look at how to prevent it by using specially tailored antibiotics.
When the harmful coliforms infect an organism, they use a protein known as intimin to attach to receptors in the intestinal wall. Intimins are located in the outer layer of the bacterium’s cell membrane, with some extending beyond the cell. The extensions are divided into five subdomains reminiscent in structure of five beads on a string.
Not much was known about the two closest to the bacterium until Julia Weikum and her colleagues identified their nuclear structures, and it was assumed that they probably were quite alike in terms of their form and structure.
“However, Julia has shown that the subdomains were different as regards their form and flexibility. The two closest to the bacterium, i.e. the base of the string of pearls, are more rigid, whereas the last three are more flexible. Specifically, this means that intitims can reach further when looking for a receptor to bind to. It is therefore probably even more effective at infecting an organism than previously thought, and this is important knowledge when it comes to developing new methods to fight coliform infections,” says Professor Preben Morth from DTU Bioengineering, who acted as Julia Weikum’s supervisor.
The study was initiated at the Centre for Molecular Medicine Norway (NCMM), a Nordic EMBL Partnership node, and completed at DTU Bioengineering. The study is funded by the international Nordforsk foundation, which primarily funds and facilitates research cooperation in the Nordics.
This article orginally appeared on the DTU.dk website. View the original article.