Many bacterial species colonize the human body. Some people get sick and are treated with antibiotics. The problem: even harmless or useful bacteria are decimated and the microbial balance is disrupted – with lasting consequences. Researchers at the University of Constance have now discovered and developed a class of compounds that deliberately eliminate pathogens without damaging other bacteria.
Constance – Antibiotics are important for the treatment of infectious diseases, but they leave a devastating trace in the human microbiome. Gastrointestinal disorders after antibiotic treatment remain the most inoffensive consequences. Because there is also the danger that after antibiotic treatment, resistant pathogens in the body, who survived the treatment – especially if the intake of the drug is interrupted prematurely. These pathogens can later cause serious infectious diseases or lead to chronic diseases.
But not all germs are dangerous. On the contrary, many microorganisms live in peace with us and are even essential to human health. The man is a true microcosm and hosts even more microbes than human cells. But this ecosystem, the human microbiome, is fragile.
Antibiotics disrupt the delicate balance because they do not distinguish between beneficial microbes and diseased microbes. If the microbiome is damaged by incorrect or too powerful medications, it can have serious consequences: allergies, obesity, inflammatory bowel disease and even psychiatric illnesses. In order to maintain the ecological diversity of bacteria specific to the body in the case of an infectious disease, it is necessary to have drugs that specifically inhibit pathogens.
From the messenger to the antibiotic
A research team led by the chemist dr. Thomas Böttcher and the biologist Prof. dr. Christof Hauck, from the University of Constance, discovered the unexplored natural antibiotic properties of a natural product that was once thought to be a bacterial signaling molecule. The signal substance of the bacterium Pseudomonas aeruginosa very selectively inhibited the growth of the pathogen Moraxella catarrhalis. The pathogen is particularly responsible for middle ear infections in children and infections in patients with chronic obstructive pulmonary disease.
Based on the natural product, scientists have developed synthetic derivatives that have demonstrated surprisingly high efficacy against M. catarrhalis. However, it was much more important that the new class of compounds have a particularly high selectivity: the drugs only inhibit the growth of M. catarrhalis, but not that of other bacteria. Even closely related species of the same genus have remained completely intact.
The Böttcher and Hauck team is currently studying the mode of action of these highly selective antibiotics against the pathogen M. catarrhalis. Antibiotics with such species selectivity would allow precision interventions to target pathogens without harming the biodiversity of beneficial microbes.
Would you like to know more about "multi-resistant germs"? Then visit our "Antibiotic Resistance" folder where we have compiled articles on important advances in medical research.
Advance also against malaria in perspective
In another recent publication of the journal Chemical Communications, the research team of Thomas Böttcher and PhD student Dávid Szamosvári, as well as scientists from Duke University (USA), succeeded in point highly selective drugs against the pathogen of malaria.
Once again, the team used the example of nature to create new, yet unexplored, quinolone nuclei systems. An association has been shown to be extremely specific for a critical phase of the life cycle of the malaria parasite. This first is tucked into the liver before it starts attacking blood cells. In this stage of the liver, the researchers were able to attack the targeted parasite and extinguish it. Their findings should help to open up new classes of chemical structures for targeted research and possible selective malaria treatment.
D. Szamosvari, T. Schuhmacher, C. Hauck, T. Böttcher: A thiochromenone antibiotic derived from the Pseudomonas quinolone signal targets the Gram-negative pathogen Moraxella catarrhalis, Chem. 10: 6624-6628 (2019); DOI: 10.1039 / c9sc01090d
D. Szamosvari, K. Sylvester, P. Schmid, KY. Lu, E.R. Derbyshire, T. Böttcher: Quanolone-alkyl tandem cyclization provides access to tricyclic pyrrolo[1,2-a]Quinoline-5-one with potent antiprotozoal activity, Chem. Common. 55: 7009-7012 (2019); DOI: 10.1039 / C9CC01689A