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 beta-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.
Mallorquí-Fernández
Goretti
G
Institut de Biologia Molecular de Barcelona, Centre d'Investigacio i Desenvolupament CSIC, C/Jordi Girona, 18-26; E-08034 Barcelona, Spain.
Marrero
Aniebrys
A
García-Piquè
Sonia
S
García-Castellanos
Raquel
R
Gomis-Rüth
F Xavier
FX
D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D016106:Methicillin Resistance; D008958:Models, Molecular; D017510:Protein Folding; D013210:Staphylococcus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins