New project aims to find better weapons against life-threating multi-resistant bacteria

A Norwegian-Danish project aims to find better weapons against life-threating multi-resistant bacteria.

Although they are microscopically small, they are the cause of huge problems. Bacteria that have become multiresistant - i.e. resistant to more than one existing type of antibiotic - are regarded as one of the most serious risks to health in the world today.

The latest bad news is that multiresistance is spreading rapidly through the group known as Gram-negative bacteria (see Fact-box). This large family, to which Escherichia coli belongs, includes resistant strains of several microbial species that are capable of producing severe chronic infections. Blood poisoning (sepsis) and the state of shock which may follow sepsis (septic shock), which are caused by such infections, account for some 135,000 deaths in Europe and 215,000 in the USA.

As one facet of the struggle to overcome these resistant bacteria, the Danish company Xellia Pharmaceuticals, SINTEF and Statens Serum Institut in Denmark aim to develop new, improved antibiotics via a research programme financially supported by the Research Council of Norway.

"Many lives will be saved if we succeed," says Grethe Evensen, Principal research scientist at Xellia.

Help from soil bacteria

Antibiotics are chemical compounds that in particular are produced by soil bacteria. In nature, microbes use such chemicals when they are fighting other microorganisms for survival and access to nutrition. A soil bacterium also plays the leading role in the four-year Norwegian-Danish project.

For 70 years, this species has served society by providing us with a wide range of chemical substances known as polymyxins - one of two types of antibiotic that still work on multiresistant bacteria from the Gram-negative family. However, polymyxins have side-effects, in that they affect kidney function, which means that they are far from ideal as a long-term treatment of chronic infections.

The members of the project hope, among other things, that they will be able to develop new antibiotics, with fewer side-effects from these faithful bacteria. They will also be studying what other substances with antibiotic effects they can persuade them to produce.

Efficient and sensitive equipment

One of the challenges involved concerns triggering the production of new substances in the bacteria, while another centres on characterising these. Xellia is being supported in both of these aspects by SINTEF and the Serum Institute.

In the project, SINTEF uses robotized instruments that allow bacteria to be cultivated under a wide range of conditions, with the aim of provoking the production of new antibiotic substances.

Research Director Håvard Sletta at SINTEF Materials and Chemistry explains that a single instrument set-up is capable of analysing several thousand samples very rapidly, in order to measure the ability of the substances to kill resistant bacteria. SINTEF also has advanced equipment that identifies the unique chemical "fingerprint" of substances that the scientists wish to examine in detail.

"This combination of automated methods and advanced analytical instruments makes our research highly efficient," says Sletta.

High-risk project

Xellia's Grethe Evensen says that the aim of the project is to develop at least one new antibiotic. However, she emphasises that since this is a research project, it is not given in advance that their efforts will be successful.

"The Research Council of Norway is contributing the risk-sharing, and that was a decisive factor in our decision to start this project," says Evensen.

"What do you think are the chances of reaching your goal?"

"As the world's biggest producer of polymyxins, we have both the experience and capacity needed to develop similar but new antibiotics with fewer side-effects. We have partners who are specialists in fermentation development, advanced analytical methods and pharmaceutical testing, and we ourselves have solid experience in the development of pharmaceuticals. All this means that we have a strong belief that the work we have started will be successful.