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"AntiResist" could shift antibiotics research paradigm

At the end of 2019, the University of Basel has received the grant to establish the new National Center of Competence in Research (NCCR) “AntiResist”, directed by Prof. Christoph Dehio from the Biozentrum. Researchers at the Biozentrum, the University Hospital, the Department of Biomedicine and the D-BSSE will establish a unique interdisciplinary center for the development of new strategies in the fight against antibiotic-resistant pathogens. The Federal Government is supporting the program with CHF 17 mio. in its initial funding phase."

Why has the problem of antibiotic-resistant pathogens become so urgent?
Antibiotic-resistant bacteria are not a new problem. After the market launch of an antibiotic, they usually appear within a few years. Until recently, there was still a sufficiently large arsenal of effective antibiotics to ensure successful therapy. In recent years, however, there has been an increase in multidrug resistant pathogens, which severely limit treatment options – and in individual cases such infections can no longer be treated.

What does this mean?
Antibiotic resistance has far-reaching consequences in everyday clinical practice. It has become a serious risk factor in routine medical interventions such as operations, cancer therapies or organ transplantation. So-called antibiotic stewardship programs can help to implement more targeted use of antibiotics that are still effective and thus limit the spread of multidrug resistance. In order to keep multidrug resistant bacteria in check in the longer term, however, new antibiotics are simply indispensable.

How do you tackle this problem with the NCCR?
With AntiResist we want to contribute to a fundamental reorientation of antibiotics research. Conventional antibiotic development is based on bacteria cultured under artificial laboratory conditions. However, after great initial successes, this research approach has been exhausted and there has been no antibiotic with fundamentally new mechanisms of action launched on the market in recent decades.

What will you do differently in your project?
Primarily, we want to investigate the bacterial living conditions within patient tissue, as these are fundamentally different from the artificial growth conditions in the laboratory used for drug development so far. If we gain a better understanding of the special conditions in patient tissue, completely new targets for innovative antibiotics will emerge. As part of AntiResist, we want to identify the Achilles' heel of the pathogens and use this knowledge to develop new antibiotics.

You will work closely with the University Hospital as part of the NCCR. What kind of collaboration will this be?
In order to elucidate the physiology of the pathogens in the patient, we first need infected patient tissue, which is provided by the University Hospital from ongoing clinical studies. Assisted by ultra-sensitive analysis methods, we want to identify important biomarkers and obtain physiological data that provide a picture of the living conditions of the pathogens in the patient. We can then use this knowledge to develop human tissue culture models that faithfully reproduce these living conditions of the bacteria in the patient.

In a further step, you are planning to collaborate with bioengineers from the Department of Biosystems Science and Engineering of the ETH Zurich in Basel (D-BSSE ). What is their task? 
Our partners from the D-BSSE will further develop the human tissue models generated by us to meet the special requirements for drug development - by the miniaturization and parallelization of the processes. The aim of the bioengineers is to establish a high-throughput screening platform that enables the automated screening of chemical libraries, which is the first step in drug development.

The last years many companies have discontinued antibiotic research. Why?
The main reason is that the current market model simply does not work. It is not profitable for the companies to invest in this field. It has been over thirty years since an antibiotic with a really novel mode of action has been developed and patents have all long expired. Today, antibiotics are largely produced in China and India and sold at very low prices. New drugs must still be able to compete in price with these cheap and, due to antibiotic resistance, increasingly ineffective drugs. And this, even though antibiotics really cure, and not only prolong survival for a few months, as is the case with some other treatments including some very expensive cancer therapies.

Will you be able to find a company prepared to bring a new drug onto the market?
The biggest danger at the moment is that loss of innovation is the price we pay until the market mechanisms are up and running again. So, it is important to push innovation during such a phase. And luckily, there are still a few pharmaceutical companies that continue research and development in the antibiotic sector, for example Roche, that we have incorporated as a collaborative partner in the AntiResist project.

Will the market adapt fast enough, to enable potential innovations from AntiResist to make it to the market?
It is evident that there is much activity going on in this area. And I think the timing is right. If we can fuel innovation now, hopefully enough changes in the market have taken place by the time new, fundamental discoveries have been made, to make it possible for these innovations to be seized and further developed. In this regard I am very confident.