Multi-drug resistant phenotype formation creates global severe clinical threat among the most important challenges facing medicine today, dictating an urgent need for novel approaches. We aim to reveal the scope and mechanisms of resistance in pathogens, by studies that have not been pursued so far worldwide. In parallel we initiated innovative research towards understanding the ribosome origin, aiming at illuminating the transition from the primordial RNA world to the contemporary coded translation era, alongside exploring new targets and providing useful clues for antibiotics design. We base our interdisciplinary objectives on our discoveries originating from the ribosomes high resolution structures, the results of our pioneering efforts and subsequent perseverance.By revealing unique properties of genuine pathogens that facilitate their exclusive resistance pathways,instead of depending solely on benign eubacterial models, we expect to gain matchless new insights. As no crystals of ribosomes from pathogens are available, we have initiated crystallographic studies, and present here preliminary results on two pathogenic life threatening bacteria, Staphylococcus aureus (associated with MRSA resistance) and Mycobacterium tuberculosis via Mycobacterium smegmatis that serve as its medical diagnostic tool. We also aim at experimentally defining the intra-ribosome region suggested by us to be a vestige of a prebiotic apparatus (proto-ribosome) by designing autonomous molecular entities with catalytic capabilities. Constructs the bind substrates have already been obtained. The expected enhancement in understanding peptide bond formation should lead to novel insights into this universal essential process. Our studies are designed to provide unprecedentedly powerful new tools for minimizing pathogens resistance thus should be of immense therapeutic relevance & will open up new horizons for researchers seeking response to challenges of the increasing antibiotic resistance.