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Antibiotics Targeting the 30S Ribosomal Subunit: A Lesson from Nature to Find and Develop New Drugs

[ Vol. 18 , Issue. 24 ]

Author(s):

Anna Maria Giuliodori*, Roberto Spurio, Pohl Milón and Attilio Fabbretti   Pages 2080 - 2096 ( 17 )

Abstract:


The use of antibiotics has revolutionized medicine, greatly improving our capacity to save millions of lives from otherwise deadly bacterial infections. Unfortunately, the health-associated benefits provided by antibiotics have been counteracted by bacteria developing or acquiring resistance mechanisms. The negative impact to public health is now considered of high risk due to the rapid spreading of multi-resistant strains. More than 60 % of clinically relevant antibiotics of natural origin target the ribosome, the supramolecular enzyme which translates the genetic information into proteins. Although many of these antibiotics bind the small ribosomal subunit, only a few are reported to inhibit the initiation of protein synthesis, with none reaching commercial availability. Counterintuitively, translation initiation is the most divergent phase of protein synthesis between prokaryotes and eukaryotes, a fact which is a solid premise for the successful identification of drugs with reduced probability of undesired effects to the host. Such a paradox is one of its kind and deserves special attention. In this review, we explore the inhibitors that bind the 30S ribosomal subunit focusing on both the compounds with proved effects on the translation initiation step and the underreported translation initiation inhibitors. In addition, we explore recent screening tests and approaches to discover new drugs targeting translation.

Keywords:

Antibiotics, Ribosome, 30S ribosomal subunit, Protein synthesis, Translation initiation, Screening tests, Drug discovery.

Affiliation:

School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Centre for Research and Innovation, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas (UPC), Lima 15023, Peru, School of Biosciences and Veterinary Medicine, University of Camerino, Camerino

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