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Chapter 21 : Inhibitor of Isoleucyl-tRNA Synthetase

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Inhibitor of Isoleucyl-tRNA Synthetase, Page 1 of 2

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Abstract:

Mupirocin was isolated as the major component of a family of structurally related antibiotics produced by a strain of Pseudomonas fluorescens. The chemical structure of mupirocin, 9-[2(E)4-(2S,3R,4R,5S)[5-(2,3-epoxy-5-hydroxy-4-methylhexyl)-3,4-dihydroxytetrahydropyran-2yl]-3-methylbut-2-enoyloxy]nonanoic acid, was established based on nuclear magnetic resonance spectroscopy, mass spectrometry, and chemical degradative studies of its methyl ester and various derivatives. Mupirocin inhibits the growth of staphylococci (including methicillin-resistant strains) and streptococci (except enterococci) at low concentrations and is bactericidal at high concentrations, which are readily achieved by topical application. Mupirocin has no cross-resistance to existing antibacterial agents, is most active at acidic pHs against bacteria included in its spectrum, and penetrates well into superficial layers of the skin and nasal mucosa. Mupirocin has been successfully used in eradication of the nasal carrier state of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Patients with folliculitis, furunculosis, impetigo, or other primary skin infections have been treated successfully with mupirocin. Mupirocin is an analogue of isoleucine; it competitively binds Isoleucyl-tRNA synthetase (IleRS) joins isoleucine to tRNA at its synthetically active site. The 2.2Å-resolution crystal structure of S. aureus IleRS complexed with tRNAIle and mupirocin has recently been solved. Mupirocin resistance in S. aureus results from changes in the target enzyme, IleRS. These resistant strains can be divided arbitrarily into two distinct groups, those which exhibit a low level of resistance and those which exhibit a high level of resistance.

Citation: Mascaretti O. 2003. Inhibitor of Isoleucyl-tRNA Synthetase, p 285-288. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch21
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Figures

Image of Figure 21.1
Figure 21.1

Chemical structure of mupirocin.

Citation: Mascaretti O. 2003. Inhibitor of Isoleucyl-tRNA Synthetase, p 285-288. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch21
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Image of Figure 21.2
Figure 21.2

Interaction of mupirocin and 2S,3S- or (L)-isoleucine with the isoleucinebinding site on IleRS.

Citation: Mascaretti O. 2003. Inhibitor of Isoleucyl-tRNA Synthetase, p 285-288. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch21
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References

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