Antibiotics Targets, Mechanisms and Resistance

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.

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