Staphylococcal methicillin resistance: Fine focus on folds and functions

Globalisation has entailed a massive increase in trade and human mobility facilitating the rapid spread of infectious agents, including those that are drug resistant. A particularly serious threat to human health is posed by methicillin-resistant staphylococcal strains which have acquired molecular mechanisms to evade the action of β-lactam antibiotics (BLAs). Full expression of high-level methicillin resistance involves a complex network of molecules and depends primarily on sufficient expression of a penicillin-binding protein with low sensitivity towards BLAs. Other factors include the fine-tuned regulation of autolytic activity of cell-wall components, as well as an optimal rate of peptidoglycan precursor formation and a highly specific peptidoglycan precursor structure. Three-dimensional structural data are available on several of the pieces involved in the jigsaw puzzle and provide a molecular basis for the understanding of methicillin resistance and for the design of new therapeutic strategies. © 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.This study was supported by grants BIO2000-1659 and BIO2003-00132 from the Spanish Ministry for Science and Technology. R.G.C. is recipient of an FPI Ph.D.-fellowship from the Spanish Ministry for Science and Technology. A.M. acknowledges a postgraduate fellowship from >Fundación Carolina>, Spanish Ministry of Foreign AffairsPeer Reviewe