Year: 2013
Type: review
Abstract: Peptidoglycan is the main component of the bacterial cell wall. It is a complex, three-dimensional mesh that surrounds the entire cell and is composed of strands of alternating glycan units crosslinked by short peptides. Its biosynthetic machinery has been, for the past five decades, a preferred target for the discovery of antibacterials. Synthesis of the peptidoglycan occurs sequentially within three cellular compartments (cytoplasm, membrane, and periplasm), and inhibitors of proteins that catalyze each stage have been identified, although not all are applicable for clinical use. A number of these antimicrobials, however, have been rendered inactive by resistance mechanisms. The employment of structural biology techniques has been instrumental in the understanding of such processes, as well as the development of strategies to overcome them. This review provides an overview of resistance mechanisms developed toward antibiotics that target bacterial cell wall precursors and its biosynthetic machinery. Strategies toward the development of novel inhibitors that could overcome resistance are also discussed.
Source: Protein Science
DOI: 10.1002/pro.2414
Authors: I. Nikolaidis, S. Favini‐Stabile, A. Dessen
Institutions: Centre National de la Recherche Scientifique, Utrecht University, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Institut de Biologie Structurale, Université Grenoble Alpes, Brazilian Center for Research in Energy and Materials, Brazilian Biosciences National Laboratory
Language: English
Subfield: Microbiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2172095238