Ada E. Yonath

Next Generation Species Specific Eco Friendly Antibiotics and Thoughts About Origin of Life


Abstract

Resistance to antibiotics is a severe problem in contemporary medicine. Many antibiotics inhibit protein biosynthesis by hampering the ribosome function. Structures of bacterial ribosomes in complex with these antibiotics illuminated common pathways of antibiotics inhibitory action, but not the species-specific diversity in infectious-diseases susceptibility. However, although pathogenicity is not linked to ribosomes, recent structures of ribosome from a multi-resistant pathogenic bacterium revealed novel structural motifs, essential to cellular protein biosynthesis but are not located in the primary ribosomal active sites, hence no mechanism for mutations leading to resistance of these sites is currently known. Thus, these findings led to the design of antibiotics with desired properties that can be optimized in terms of their chemical properties, toxicity, penetration, species-specificity, thus preserving the microbiome. They can also be optimized in terms of bio degradability, thus reducing the ecological hazards caused by the spread of the current antibiotics’ non-degradable metabolites.

The internal ribosome active site, an RNA pocket where peptide bonds are being formed, is highly conserve and still functions in contemporary cells. This pocket seems to be a remnant of a prebiotic bonding apparatus, called by us the “proto ribosome” and its catalytic capabilities were recently proven by the formation of peptide bonds. This breakthrough results will be shown and the suggestion that it evolved and optimized to become the modern ribosome together with the introduction and development of the genetic code and its products, the proteins, will be discussed.

Interestingly, some of the ribosomal RNA insertions identified in eukaryotic ribosomes overlap insertions detected in ribosomes of pathogenic bacteria. Hence, raising the question: is pathogenicity a missing link between eubacteria and eukaryotes?


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