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‘Sugar detectives’ get their hooks into viruses and bacteria

Researchers at the University of Copenhagen are the first in the world to genetically engineer human cells to construct a detailed picture of the battle plan bacteria and viruses deploy when they make us ill. This discovery may lead to new therapies, eliminating the need for antibiotics.

Bacteria and viruses have a sweet tooth! It’s no coincidence when these microorganisms attack the human organism to make us ill, for example when they give us pneumonia or flu. The great majority, around 80%, of these bacteria and viruses seek out the sugars on the surface of our cells. They then settle and start to attack the cell.

To a certain extent, the chemical composition of this ‘sugar coating’ varies from cell type to cell type. This means that a bacterium or a virus will only seek out specific cells – those on which they are able to settle.

So, if we know which types of cell the microorganisms will settle on, we can build a detailed picture of the battle plan of a specific bacterium or virus. Using this method to map a very large number of bacteria and viruses gives us a more holistic view of the microorganisms that cause disease as well as their rampage through the human body.

And this is where a team of scientists from the basic research centre Copenhagen Center for Glycomics (CCG) at the University of Copenhagen, together with colleagues from the USA and the Netherlands, have achieved something unprecedented:

They have succeeded in creating an entire library of gene engineered human cells – ‘sugar detectives’ that can get their hooks into the viruses and bacteria that make us ill.
This discovery was recently published in the online version of the scientific journal Molecular Cell, and the research underlying the finding was mainly funded by the Lundbeck Foundation.

Manipulated cells
The researchers at CCG worked with human laboratory cells typically used in drug design, and gene engineering was key to their work. First author of the scientific article, Yoshiki Narimatsu, explains further:

‘We all have a large number and a great variety of sugars in our body. They sit on the outside of our cells like hooks that bacteria and viruses can latch onto. And we used gene engineering on these sugar molecules to generate our cell library.

There are around 400 genes in human DNA that regulate these sugars. The research team manipulated an immense number of human cells so that each one switched off one of the 400 genes. These manipulated cells form the backbone of the library. But how does it work?

Professor Henrik Clausen from CCG, who headed the research team, explains that it is probably easiest to understand if we imagine a bucket:

‘If we put all of these manipulated cells into a bucket and then add a mix of viruses and pathogenic bacteria, we would get a precise picture of which microorganisms bind to which cells and to which sugars. That’s not exactly how it works in the lab, but it’s actually the basic principle.’

New therapies
The sugars on our cells, to which bacteria and viruses bind, are interesting in a wide variety of contexts. When cancer cells spread, for instance, some of them play key roles.

We can also manipulate sugar molecules to design various therapies. They can be used, for example, to inhibit infections. As was the case with the high-profile Tamiflu drug, which arrived on the scene when an epidemic of avian flu threatened the western world a few years ago.

In the long term, it is not impossible to imagine that the cell library will play a role in the future in the design of drugs to inhibit pathogenic microorganisms – without the antibiotic effect, and Henrik Clausen goes on to explain:

‘And, down the road, it’s highly conceivable that the knowledge contained in the library will have a huge impact on how we direct our gut flora – the microbiome – in various directions. For example, to prevent and combat infectious diseases.’

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