How antibiotics interact

Date:
August 31, 2020
Source:
University of Cologne
Summary:
Understanding bottleneck effects in the translation of bacterial
proteins can lead to a more effective combination of antibiotics.



FULL STORY ==========================================================================
It is usually difficult to predict how well drugs will work when they are combined. Sometimes, two antibiotics increase their effect and inhibit
the growth of bacteria more efficiently than expected. In other cases,
the combined effect is weaker. Since there are many different ways
of combining drugs - - such as antibiotics -- it is important to be
able to predict the effect of these drug combinations. A new study
has found out that it is often possible to predict the outcomes of
combining certain antibiotics by quantitatively characterizing how
individual antibiotics work. That is the result of a joint study by
Professor Tobias Bollenbach at the University of Cologne with Professor
Gasper Tkacik and the doctoral researcher Bor Kavcic at the Institute of Science and Technology Austria. The paper 'Mechanisms of drug interactions between translation-inhibiting antibiotics' has been published in Nature Communications.


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'We wanted to find out how antibiotics that inhibit protein synthesis in bacteria work when combined with each other, and predict these effects
as far as possible, using mathematical models,' Bollenbach explained. As
head of the research group 'Biological Physics and Systems Biology'
at the University of Cologne, he explores how cells respond to drug combinations and other signals.

Bacterial ribosomes can gradually translate the DNA sequence of genes into
the amino acid sequence of proteins (translation). Many antibiotics target
this process and inhibit translation. Different antibiotics specifically
block different steps of the translation cycle. The scientists found
out that the interactions between the antibiotics are often caused by bottlenecks in the translation cycle. For example, antibiotics that
inhibit the beginning and middle of the translation cycle have much
weaker effects when combined.

In order to clarify the underlying mechanisms of drug interactions, the scientists created artificial translation bottlenecks that genetically
mimic the effect of specific antibiotics. If such a bottleneck is located
in the middle of the translation cycle, a traffic jam of ribosomes forms,
which dissolves upon introducing another bottleneck at the beginning of
the translation cycle. Using a combination of theoretical models from statistical physics and experiments, the scientists showed that this
effect explains the drug interaction between antibiotics that block
these translation steps.

Tobias Bollenbach concluded: 'A quantitative understanding of the effect
of individual antibiotics allows us to predict the effect of antibiotic combinations without having to test all possible combinations by trial
and error. This finding is important because the same approach can be
applied to other drugs, enabling the development of new, particularly
effective drug combinations in the long term.'

========================================================================== Story Source: Materials provided by University_of_Cologne. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Bor Kavčič, Gasper Tkačik, Tobias
Bollenbach. Mechanisms
of drug interactions between translation-inhibiting
antibiotics. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020-17734-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200831131640.htm

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