Most of the antibiotics now in use have been discovered more or less by chance, and their mechanisms of action have only been elucidated after their discovery. To meet the medical need for next-generation antibiotics, a more rational approach to antibiotic development is clearly needed.
Opening with a general introduction about antimicrobial drugs, their targets and the problem of antibiotic resistance, this reference systematically covers currently known antibiotic classes, their molecular mechanisms and the targets on which they act. Novel targets such as cell signaling networks, riboswitches and bacterial chaperones are covered here, alongside the latest information on the molecular mechanisms of current blockbuster antibiotics.
With its broad overview of current and future antibacterial drug development, this unique reference is essential reading for anyone involved in the development and therapeutic application of novel antibiotics.
Claudio Gualerzi is a full professor of Molecular Biology at the University of Camerino (Italy). For almost 20 years, he was also a research group leader at the Max-Planck-Institute for Molecular Genetics in Berlin (Germany). For his work on ribosome function and the discovery of novel antibiotics, Professor Gualerzi has received numerous awards and honorary lectureships, including the research prize of the Alexander von Humboldt foundation.
Attilio Fabbretti is a research associate in the laboratory of Molecular Biology at the University of Camerino (Italy). He received the prize of the Italian Society for General Microbiology and Microbial Biotechnology for the best PhD thesis in 2007.
Letizia Brandi is a research associate in the laboratory of Molecular Biology at the University of Camerino (Italy). Previously, she worked at the University of Montana (Missoula, USA) and at Vicuron Pharmaceuticals (Gerenzano, Italy).
Cynthia Pon is full professor of Molecular and Microbial Genetics at the University of Camerino (Italy). She has been working on the structural and functional properties of ribosomes, including the action of ribosomal antibiotics, for more than 40 years.
Table of Contents
INTRODUCTION A chemist's survey of different antibiotic classes Molecular mechanisms of antibiotic resistance Fitness costs of antibiotic resistance
TARGETS AND INHIBITORS Inhibitors of cell wall synthesis Inhibitors of membranes - influx - efflux pumps Antibiotics targeting membranes Inhibitors of cell partitioning Antibiotics interfering with cell signaling and quorum sensing Chaperone inhibitors Mechanism of action of inhibitors of bacterial type IIA topoisomerases RNA polymerase and transcription inhibitors RNase P inhibitors Riboswitches & ribozymes inhibitors Inhibitors of ribosome assembly and maturation aa-tRNA synthetases inhibitors A-site inhibitors Translation initiation & P-site inhibitors Peptidyl transferase inhibitors Translocation inhibitors Termination inhibitors Ribosome tunnel inhibitors Rib-X inhibitors Yeast translational inhibitors
OUTLOOK Natural Products in Drug Discovery Challenges of Antibiotic Discovery