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The beast and its Achilles heel:
A novel target to fight multi-resistant pathogenic bacteria
The discovery of penicillin by Alexander Fleming in 1928 and the broad application of antibiotics marked a major victory of mankind in the battle against infectious diseases.
However, shortly after the beginning of industrial penicillin production in 1942 some human pathogens already acquired resistance against penicillin and related antibiotics.
Moreover, the frequent use of antibiotics in the past and the rapid adaptation of bacteria to these compounds led to the development of many multi-resistant pathogens.
Some of the pathogenic bacteria are even resistant against most commercially available antibiotics. Therefore, both the discovery and the development of new antibacterial substances are extremely important to fight these threats of human health. Unfortunately, the pipeline of novel compounds with antibiotic activity and appropriate pharmaceutical properties is empty. This makes the challenge of finding new compounds even more urgent!
The first step in designing efficient novel antibacterial compounds is the identification of a suitable target. Very recently, a potentially interesting target has been identified. The emerging signaling molecule cyclic dinucleotide c-di-AMP is essential in the Gram-positive model organism B. subtilis and in closely related pathogenic bacteria such as Listeria monocytogenes, Streptococcus pneumoniae, and Staphylococcus aureus.
These bacteria cause serious diseases and are often multi-resistant. c-di-AMP is needed for the control of vital cellular processes in these pathogens because both: lack and accumulation of c-di-AMP, strongly inhibit growth of the bacteria.
Therefore, any substance that disturbs the homeostasis of the important signaling molecule c-di-AMP and the interaction with its target is of substantial interest to fight human pathogens. The next important step in identifying efficient antibacterial compounds, which either inhibit c-di-AMP biosynthesis or interfere with the essential function of c-di-AMP in the cell, is the development of a powerful screening system.
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