Michael Givskov – Københavns Universitet

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23. december: A deeply worrying growth in the number of multi-resistant, bacterial infections

KU's Alumneforening har bedt forskere fra Københavns Universitet om at fortælle om et af deres aktuelle forskningsprojekter. Det er tilsammen blevet til de 24 låger i årets forskningsjulekalender, hvor du kan læse om alt fra sociale medier til sorte huller.

I dagens låge fortæller Professor Michael Givskov fra Det Sundhedsvidenskabelige Fakultet om sin forskning i multiresitente bakterier.

Chronic infections

Biofilms are the central mode of microbial life, essential for all life support processes on Earth. It is becoming evident that a deeper understanding of biofilm processes will provide new and better opportunities for the development of environmentally sustainable biotechnological processes and improvement of human health. Our interest in biofilm biology is built around the observation that chronic infections are typically associated with pathogens in the biofilm mode of growth. Chronic infections share similar characteristics: they are hard to diagnose, they resist host immunity, they are difficult to eradicate with the present days armories of antibiotics and they are becoming a considerable socioeconomic burden. Health care-associated, complicating bacterial infections occur in 5-10 % of hospitalized patients and we find biofilm-infections on implants, medical equipment, such as stents, vascular prostheses, pacemakers and artificial hearts, and those associated with distinct disease states, including chronic wounds, cystic fibrosis, COPD and urinary tract infection.

I’m sure, we all know the feeling of “velvet” on our teeth and as kids we might have struggled with biofilms on the glass surfaces in our aquariums. Infections based on biofilm forming bacteria enables the bacteria to attain the highest levels of antibiotic resistance and an almost unlimited capacity to evade the host immune system (so they become chronic).

To understand, diagnose, treat and prevent chronic bacterial infections

Surprisingly, while biofilms are present everywhere and affect each and every facet of our lives, the understanding of how they are organized, how they function and how they can be controlled is currently in its infancy. As to this end, SUND has established the new Costerton Biofilm Center (CBC) at which I am the managing director. The Centre aims at the delivery of new approaches to help understand, diagnose, treat and prevent chronic bacterial infections with the intent of improved public health and economic gain. Our research also addresses major societal challenges linked to the increase in elderly, immuno-compromised and hospitalized people in parallel with the developing diabetes 2 epidemic; factors that dispose for development of chronic infections.

At the CBC, our research will pave the way for solutions to one of the most serious but also paradoxical health problems today; a deeply worrying growth in the number of multi-resistant, bacterial infections and a marked industrial slowdown in the development of new antimicrobial medicine. More than half a century ago, antibiotics were the low hanging fruits of antimicrobial drug development and we all know the problem of development of bacterial resistance to conventional antibiotics. CBC is not continuing along the line of conventional drug design. We seek new targets and new mechanisms.

We have at CBC provided evidence that bacterial cell-signaling circuits constitute attractive targets for biofilm control in infectious diseases as well as in industrial settings. Causing disease can be obstructed by jamming the bacterial signaling systems with molecular mimics of the native signals and we have delivered proof of concept for this as an antimicrobial principle. As to this, we are currently pursuing a universal controller central in the biofilm lifecycle. High internal levels of the signal molecule c-di-GMP drive bacteria to form biofilms whereas reduced c-di-GMP levels lead biofilm bacteria into dispersal where they subsequently assume the planktonic mode of life.

In response to environmental signals, a number of enzymes in the bacterial cell modulate the internal, steady state concentration of c-di-GMP. We aim at identifying chemical signals that can modulate c-di-GMP levels in bacteria and force them away from this protective state to a free-living mode. When we lower the c-di-GMP concentration to disperse biofilms, efficient eradication by means of conventional antibiotics and disinfectants (active against planktonic bacteria) can be achieved at low concentrations with obvious reduced side effects on the human host. Antimicrobials that jam signaling systems are not toxic and do not lead to selection for resistance.

Stabilizing the public expenditures on health

Academia cannot meet the expenses of taking drugs to the market, but CBC research will translate into knowledge, education, innovation incl. drug development and growth with the aim of stabilizing the public expenditures on health in close collaboration with hospitals, the pharmaceutical industry and foreign research environments of highest scientific quality. In fact, investment in this area may result in an enormous return, since there is a significant industrial angle to biofilm research. For technical applications, the removal of biofilms within e.g. oil industry, washing machines, production machinery in paper and food packaging industry, cooling water circuits, and drinking water manufacturing systems can be critical for safety and efficacy of those processes. Solution that applies to medicine may also apply to industry. In addition to creating new and exciting science and technology, these initiatives will also contribute to the new generation of truly, internationally minded and educated scientists, prepared for the multidisciplinary research efforts increasingly demanded by hospitals, academia and industry.

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