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Resistance to and synthesis of the antibiotic mupirocin
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Journal Article
Resistance to and synthesis of the antibiotic mupirocin
2010
Overview
Key Points
The spread of methicillin-resistant
Staphylococcus aureus
(MRSA) necessitates the development of new antibiotics.
The control of mupirocin production in soil bacteria is in proportion to bacterial cell density.
Mupirocin inhibits isoleucyl-tRNA synthetase, and spontaneous mupirocin-resistant mutants are generally less fit than wild-type bacteria.
Mupirocin can be used topically but not systemically owing to its rapid hydrolysis.
Mupirocin is made by a complex polyketide biosynthetic pathway.
Engineering mupirocin production
in vivo
or producing it by chemical synthesis could enable the production of new derivatives, the biological activity of which could then be explored.
Mupirocin is a polyketide antibiotic produced by
Pseudomonas fluorescens
that is used to control the carriage of methicillin-resistant
Staphylococcus aureus
. Here, Thomas and colleagues describe the mechanisms underlying the mode of action and biosynthesis of mupirocin and discuss how this understanding could lead to the development of novel antibiotics.
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Anti-Bacterial Agents - biosynthesis
/ Anti-Bacterial Agents - chemical synthesis
/ Anti-Bacterial Agents - therapeutic use
/ Biomedical and Life Sciences
/ Drug resistance in microorganisms
/ Drug Resistance, Bacterial - genetics
/ Enzymes
/ Isoleucine-tRNA Ligase - metabolism
/ Mupirocin - chemical synthesis
/ Mutation
/ Pseudomonas fluorescens - genetics
/ Pseudomonas fluorescens - metabolism
/ Virology
