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As multidrug-resistant germs become more of a threat, we need new antibiotics more than ever. Unfortunately, antibiotics can not distinguish pathogens from useful microbes. They can destroy the delicate balance of the microbiome and cause permanent damage. The research team around the chemist Thomas Boettcher has taken an important step in solving these problems. In collaboration with the team of biologist Christof Hauck, also a biologist from Constance, researchers discovered the antibiotic properties of a natural product until then considered a simple bacterial signal molecule. The team, including Drs. Dávid Szamosvári and Tamara Schuhmacher, has developed and studied synthetic derivatives of the natural substance that have been found to be surprisingly effective against the pathogen Moraxella catarrhalis. In the process, only the growth of these pathogens was inhibited, not the growth of other bacteria. In another project, the researchers managed to develop another selective agent to fight the malaria parasite. These results could lead to a new basis for new precision antibiotics. The results of the research are published in the current editions of the Chemical Science and Chemical Communications journals.
Antibiotics are important for the treatment of infectious diseases, but they leave a trail of destruction in the human microbiome. Gastrointestinal disorders following antibiotic treatments are one of the least problems in this context. Quite often, resistant pathogens replace beneficial microbes. Later, they can cause serious infectious diseases or chronic diseases. However, not all germs are dangerous. On the contrary, many microorganisms live in peaceful coexistence with us and are even vital to human health. We humans are real microcosms and host more microbes than human cells. Yet this ecosystem, the human microbiome, is fragile. Allergies, overweight, inflammatory bowel disease and even psychiatric disorders can be the result of a damaged microbiome. The question is how to maintain this ecological diversity in case of microbial infection.
The research team originally studied the signals of the bacterium Pseudomonas aeruginosa. A compound aroused their interest as it very selectively inhibited the growth of the pathogen Moraxella catarrhalis. This pathogen causes, for example, otitis media in children as well as infections in patients with chronically obstructive lung disease. The synthetic engineering of this natural product on scaffolding has given rise to a new clbad of compounds offering tremendous antibiotic efficacy. What was really surprising was the selectivity of the substance: only the growth of Moraxella catarrhalis was inhibited, not that of other bacteria. Even closely related bacteria of the same species remained completely unharmed.
Thomas Boettcher and Christof Hauck are currently studying the mechanism of action of this highly selective antibiotic against the pathogen Moraxella catarrhalis. Antibiotics with such selectivity would allow precision treatment and specifically eliminate pathogens while preserving the diversity of useful microbes.
In another ongoing project, described in the journal Chemical Communications, the research team around Thomas Boettcher and the PhD student Dávid Szamosvári, in collaboration with researchers from Duke University (USA), have succeeded in developing highly selective agents against the malaria parasite. These were also inspired by the example of Nature and the team created new quinolone ring systems, not yet described. A compound has been shown to be extremely specific at a critical stage of the life cycle of the malaria parasite. At first this parasite will settle in the liver before invading the blood cells. The researchers were able to target and eliminate the parasite at this stage of malaria. New discoveries can now be used for targeted research and the development of selective malaria therapies based on new clbades of chemical compounds.
References: D. Szamosvari, T. et al. A thiochromenone antibiotic derived from the Pseudomonas quinolone signal selectively targets the Gram-negative pathogen, Moraxella catarrhalis. Chem. Sci. (2019) DOI :: 10.1039 / c9sc01090d
D. Szamosvari, K. et al. Close the cycle to break the cycle: tandem cyclization quinolone-alkyne gives access to tricyclic pyrrolo[1,2-a]quinoline-5-ones with potent antiprotozoal activity. Chem. Common. (2019) DOI: 10.1039 / C9CC01689A
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