Resistance to and synthesis of the antibiotic mupirocin.
Mupirocin, a polyketide antibiotic produced by Pseudomonas fluorescens, is used to control the carriage of methicillin-resistant Staphylococcus aureus on skin and in nasal passages as well as for various skin infections. Low-level resistance to the antibiotic arises by mutation of the mupirocin target, isoleucyl-tRNA synthetase, whereas high-level resistance is due to the presence of an isoleucyl-tRNA synthetase with many similarities to eukaryotic enzymes. Mupirocin biosynthesis is carried out by a combination of type I multifunctional polyketide synthases and tailoring enzymes encoded in a 75 kb gene cluster. Chemical synthesis has also been achieved. This knowledge should allow the synthesis of new and modified antibiotics for the future.
Thomas
Christopher M
CM
School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Hothersall
Joanne
J
Willis
Christine L
CL
Simpson
Thomas J
TJ
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D007533:Isoleucine-tRNA Ligase / Q000378:metabolism; D016712:Mupirocin / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000627:therapeutic use*; D011551:Pseudomonas fluorescens / Q000235:genetics / Q000378:metabolism; D053038:Quorum Sensing
D000900:Anti-Bacterial Agents; D016712:Mupirocin; D007533:Isoleucine-tRNA Ligase