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New method against antibiotic resistance more effective?
Antibiotic-resistant bacterial strains are a growing problem worldwide. Conventional drug treatments with antibiotics are losing their effectiveness, and previously well-controlled diseases are suddenly posing a serious health risk. Scientists at the Ludwig Maximillians University (LMU) in Munich now collaborate with colleagues from the US discovered a possible alternative to conventional antibiotics, which should also be effective in multidrug-resistant bacteria.
"Multidrug-resistant bacteria, in which antibiotics are no longer effective, are becoming an ever greater problem in medicine," says the LMU. However, antibiotics from the group of so-called orthosomycins could remedy this situation. Because these set according to the LMU at a completely different binding site in bacteria than the other antibiotics. The research team around Dr. Daniel Wilson from the Gene Center of the LMU, Dr. med. Scott Blanchard of Cornell University (USA) and dr. Yury Polikanov from the University of Illinois at Chicago (USA) has structurally characterized two orthosomycins and revealed their mechanism of action in a recent study. The researchers published their findings in the journal "Proceedings of the National Academy of Sciences" (PNAS)..
Antibiotic-resistant bacteria are a major medical problem, but researchers have now discovered a potential new source of treatment for such infections. (Image: jarun011 / fotolia.com) New antibacterial drugs are urgently needed
With the increasing resistance to antibiotics and associated treatment difficulties, the development of new antibacterial drugs is urgently needed. "Biochemical studies suggest that so-called orthosomycin antibiotics could be an effective alternative," report the scientists of LMU. The Orthosomycins differ structurally from other antibiotics, according to the researchers. Their molecules are very long in comparison. "Like most antibiotics, orthosomycins dock to the bacterial protein factories - the ribosomes - and" prevent the production of new proteins necessary for the survival and proliferation of pathogens, "according to the LMU. However, they apparently use a different docking site of ribosomes than the other antibiotics.
Previously unknown binding site discovered
"For two of these orthosomycins, evernimicin and avilamycin, we have now investigated by means of high-resolution cryo-electron microscopic images exactly where they bind," explains study author Stefan Arenz from LMU. The researchers were able to prove that these antibiotics dock at a previously unknown binding site in the ribosome. According to the scientists, the newly discovered binding site lies in a certain turn of the ribosome and allows evernimicin and avilamycin to bind simultaneously to both ribosomal RNA and ribosomal protein. This is "a completely different binding site than other antibiotics", which is why "no cross-resistance to other antibiotics" occur, reports Stefan Arenz.
Production of proteins blocked
Using additional fluorescence resonance energy transfer (FRET) analyzes, scientists were also able to elucidate how the orthosomycins paralyze the ribosome and prevent the proliferation of bacteria. In order to synthesize proteins, so-called tRNA must first bind with one end to the ribosome and then "swing" with its other end into the active center of the ribosome, explain the scientists. Evernimicin and avilamycin block this ringing because they are in the way of tRNA, Arenz continues. In this way, protein production in the ribosome is shut down. The current findings could help to develop better drugs in the future against multidrug-resistant bacteria, the researchers hope. (Fp)