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Resistance to and synthesis of the antibiotic mupirocin

Nature Reviews Microbiology volume 8, pages 281–289 (2010)Cite this article

Subjects

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.

Abstract

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.

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Figure 1: Structures of mupirocin and thiomarinol compounds.
Figure 2: Binding of mupirocin to its target enzyme, isoleucyl-tRNA synthetase, from Staphylococcus aureus.
Figure 3: The mupirocin biosynthesis genes and the proposed pathway of mupirocin production.
Figure 4: Monic acid pyran ring formation.
Figure 5: Chemical synthesis of mupirocin analogues.

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References

  1. Fuller, A. T. et al. Pseudomonic acid: an antibiotic produced by Pseudomonas fluorescens. Nature 234, 416–417 (1971).

    Article  CAS  PubMed  Google Scholar 

  2. Fritz, E., Fekete, A., Lintelmann, J., Schmitt-Kopplin, P. & Meckenstock, R. U. Isolation of two Pseudomonas strains producing pseudomonic acid A. Syst. Appl. Microbiol. 32, 56–64 (2009).

    Article  CAS  PubMed  Google Scholar 

  3. Stierle, D. B. & Stierle, A. A. Pseudomonic acid derivatives from a marine bacterium. Cell. Mol. Life Sci. 48, 1165–1169 (1992).

    Article  CAS  Google Scholar 

  4. Clayton, J. P., Oliver, R. S., Rogers, N. H. & King, T. J. Chemistry of pseudomonic acid. 3. Rearrangement of pseudomonic acid A in acid and basic solution. J. Chem. Soc. Perkin Trans. 1 1979, 838–846 (1979).

    Article  Google Scholar 

  5. Hughes, J. & Mellows, G. Inhibition of isoleucyl-transfer ribonucleic-acid synthetase in Escherichia coli by pseudomonic acid. Biochem. J. 176, 305–318 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nakama, T., Nureki, O. & Yokoyama, S. Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase. J. Biol. Chem. 276, 47387–47393 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Silvian, L. F., Wang, J. M. & Steitz, T. A. Insights into editing from an Ile-tRNA synthetase structure with tRNAIle and mupirocin. Science 285, 1074–1077 (1999). The crystal structure of IleRS with mupirocin bound provides a clear framework for understanding the molecular interaction of the antibiotic with its target.

    Article  CAS  PubMed  Google Scholar 

  8. Brown, M. J. et al., Rational design of femtomolar inhibitors of isoleucyl tRNA synthetase from a binding model for pseudomonic acid-A. Biochemistry 39, 6003–6011 (2000).

    Article  CAS  PubMed  Google Scholar 

  9. Farmer, T. H., Gilbart, J. & Elson, S. W. Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus. J. Antimicrob. Chemother. 30, 587–596 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Antonio, M., McFerran, N. & Pallen, M. J. Mutations affecting the Rossman fold of isoleucyl-tRNA synthetase are correlated with low-level mupirocin resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 46, 438–442 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hurdle, J. G., O'Neill, A. J., Ingham, E., Fishwick, C. & Chopra, I. Analysis of mupirocin resistance and fitness in Staphylococcus aureus by molecular genetic and structural modelling techniques. Antimicrob. Agents Chemother. 48, 4366–4376 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yanagisawa, T., Lee, J. T., Wu, H. C. & Kawakami, M. Relationship of protein structure of isoleucyl-transfer-RNA synthetase with pseudomonic acid resistance of Escherichia coli. A proposed mode of action of pseudomonic acid as an inhibitor of isoleucyl-t-RNA synthetase. J. Biol. Chem. 269, 24304–24309 (1994).

    CAS  PubMed  Google Scholar 

  13. Jenal, U. et al. Isoleucyl-transfer RNA-synthetase of Methanobacterium thermoautotrophicum Marburg. Cloning of the gene, nucleotide sequence, and localization of a base change conferring resistance to pseudomonic acid. J. Biol. Chem. 266, 10570–10577 (1991).

    CAS  PubMed  Google Scholar 

  14. Nascimento, M. M., Lemos, J. A., Abranches, J., Lin, V. K. & Burne, R. A. Role of RelA of Streptococcus mutans in global control of gene expression. J. Bacteriol. 190, 28–36 (2008).

    Article  CAS  PubMed  Google Scholar 

  15. Paulander, W., Maisnier-Patin, S. & Andersson, D. I. Multiple mechanisms to ameliorate the fitness burden of mupirocin resistance in Salmonella typhimurium. Mol. Microbiol. 64, 1038–1048 (2007). An important approach to considering why mupirocin resistance can cause a burden to its host and is therefore not as widespread as it might be.

    Article  CAS  PubMed  Google Scholar 

  16. Sutherland, R. et al. (1985). Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob. Agents Chemother. 27, 495–498 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yanagisawa, T. & Kawakami, M. How does Pseudomonas fluorescens avoid suicide from its antibiotic pseudomonic acid? Evidence for two evolutionarily distinct isoleucyl-tRNA synthetases conferring self-defense. J. Biol. Chem. 278, 25887–25894 (2003). A biochemical description of the properties of the two IleRS proteins that are encoded by mupirocin-producing bacteria.

    Article  CAS  PubMed  Google Scholar 

  18. Hodgson, J. E. et al. Molecular characterization of the gene encoding high-level mupirocin resistance in Staphylococcus aureus J2870. Antimicrob. Agents Chemother. 38, 1205–1208 (1994). A key study that identifies high-level resistance in S. aureus as being due to a second IleRS protein that is encoded by a plasmid.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Beighton, D. et al. Isolation and identification of Bifidobacteriaceae from human saliva. Appl. Environ. Microbiol. 74, 6457–6460 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. El-Sayed, A. K. et al. Characterization of the mupirocin biosynthesis gene cluster from Pseudomonas fluorescens NCIMB 10586. Chem. Biol. 10, 419–430 (2003). A description of the genetic organization of the mup cluster, identifying it as one of the first two trans -acyltransferase type I polyketide synthase systems.

    Article  CAS  PubMed  Google Scholar 

  21. Patel, J. B., Gorwitz, R. J. & Jernigan, J. A. Mupirocin resistance. Clin. Infect. Dis. 49, 935–941 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Perkins, D., Hogue, J. S., Fairchok, M., Braun, L. & Viscount, H. B. Mupirocin resistance screening of methicillin-resistant Staphylococcus aureus isolates at Madigan Army Medical Center. Mil. Med. 173, 604–608 (2008).

    Article  PubMed  Google Scholar 

  23. Simor, A. E. et al. Mupirocin-resistant, methicillin-resistant Staphylococcus aureus strains in Canadian hospitals. Antimicrob. Agents Chemother. 51, 3880–3886 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Perez-Roth, E., Lopez-Aguilar, C., Alcoba-Florez, J. & Mendez-Alvarez, S. High-level mupirocin resistance within methicillin-resistant Staphylococcus aureus pandemic lineages. Antimicrob. Agents Chemother. 50, 3207–3211 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sareyyupoglu, B., Ozyurt, M., Hanzedaroglu, T. & Ardic, N. Detection of methicillin and mupirocin resistance in staphylococcal hospital isolates witha touchdown multiplex polymerase chain reaction. Folia Microbiol. (Praha) 53, 363–367 (2008). An important demonstration of the value of rapid PCR techniques for identifying resistance genes and highlighting the prevalence of mupA , a gene conferring high-level mupirocin resistance.

    Article  CAS  Google Scholar 

  26. Malaviolle, X., Nonhoff, C., Denis, O., Rottiers, S. & Struelens, M. J. Evaluation of disc diffusion methods and Vitek 2 automated system for testing susceptibility to mupirocin in Staphylococcus aureus. J. Antimicrob. Chemother. 62, 1018–1023 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Carre, N. et al. Staphylococcus aureus carrying Panton-Valentine leukocidin genes nasal colonization and skin infection: screening in case of outbreak in a school environment. Med. Mal. Infect. 38, 483–488 (2008) (in French).

    Article  CAS  PubMed  Google Scholar 

  28. Price, C. S. et al. Staphylococcus aureus nasal colonization in preoperative orthopaedic outpatients. Clin. Orthop. Relat. Res. 466, 2842–2847 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  29. van Rijen, M. M. L., Bonten, M., Wenzel, R. P. & Kluytmans, J. Intranasal mupirocin for reduction of Staphylococcus aureus infections in surgical patients with nasal carriage: a systematic review. J. Antimicrob. Chemother. 61, 254–261 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. Ha, K. R., Psaltis, A. J., Butcher, A. R., Wormald, P. J. & Tan, L. W. In vitro activity of mupirocin on clinical isolates of Staphylococcus aureus and its potential implications in chronic rhinosinusitis. Laryngoscope 118, 535–540 (2008).

    Article  PubMed  Google Scholar 

  31. Coates, T., Bax, R. & Coates, A. Nasal decolonization of Staphylococcus aureus with mupirocin: strengths, weaknesses and future prospects. J. Antimicrob. Chemother. 64, 9–15 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Drake, D. R., Brogden, K. A., Dawson, D. V. & Wertz, P. W. Thematic review series: skin lipids. Antimicrobial lipids at the skin surface. J. Lipid Res. 49, 4–11 (2008).

    Article  CAS  PubMed  Google Scholar 

  33. Alfonso, K., Collazo, M., Fernandez, M. & Ballagas, C. Cost-efficacy analysis of topical ozonized oil versus mupirocin cream in the treatment of impetigo. Lat. Am. J. Pharm. 27, 512–518 (2008).

    Google Scholar 

  34. McConeghy, K. W., Mikolich, D. J. & LaPlante, K. L. Agents for the decolonization of methicillin-resistant Staphylococcus aureus. Pharmacotherapy 29, 263–280 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Lee, D. K. et al. Antimicrobial activity of mupirocin, daptomycin, linezolid, quinupristin/dalfopristin and tigecycline against vancomycin-resistant enterococci (VRE) from clinical isolates in Korea (1998 and 2005). J. Biochem. Mol. Biol. 40, 881–887 (2007).

    CAS  PubMed  Google Scholar 

  36. Feline, T. C., Jones, R. B., Mellows, G. & Phillips, L. Pseudomonic acid. Part 2. Biosynthesis of pseudomonic acid A. J. Chem. Soc. Perkin Trans. 1 1977, 309–318 (1977).

    Article  Google Scholar 

  37. Whatling, C. A. et al. Identification of a 60-Kb region of the chromosome of Pseudomonas fluorescens NCIB-10586 required for the biosynthesis of pseudomonic acid (mupirocin). Microbiology 141, 973–982 (1995).

    Article  CAS  Google Scholar 

  38. Wu, J. et al. In vivo mutational analysis of the mupirocin gene cluster reveals labile points in the biosynthetic pathway: the “leaky hosepipe” mechanism. Chembiochem 9, 1500–1508 (2008). An important description of a model that may help to understand how polyketide synthase factories function as production lines that start to shed intermediates at several points if the normal flow is interrupted.

    Article  CAS  PubMed  Google Scholar 

  39. Martin, F. M. & Simpson, T. J. Biosynthetic-studies on pseudomonic acid (mupirocin), a novel antibiotic metabolite of Pseudomonas fluorescens. J. Chem. Soc. Perkin Trans. 1 1989, 207–209 (1989).

    Article  Google Scholar 

  40. Cheng, Y. Q., Tang, G. L. & Shen, B. Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis. Proc. Natl Acad. Sci. USA 100, 3149–3154 (2003). The first characterization of a discrete, iteratively acting acyltransferase that loads malonyl coA in trans onto type I acyltransferase-less polyketide proteins.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bumpus, S. B., Magarvey, N. A., Kelleher, N. L., Walsh, C. T. & Calderone, C. T. Polyunsaturated fatty-acid-like trans-enoyl reductases utilized in polyketide biosynthesis. J. Am. Chem. Soc. 130, 11614–11616 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Nguyen, T. et al. Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection. Nature Biotech. 26, 225–233 (2008).

    Article  CAS  Google Scholar 

  43. Wu, J. et al. Mupirocin H, a novel metabolite resulting from mutation of the HMG-CoA synthase analogue, mupH in Pseudomonas fluorescens. Chem. Commun. (Camb.) 20, 2040–2042 (2007). The first description of a metabolite related to monic acid that is not condensed with 9-hydroxynonanoic acid or a related product.

    Article  Google Scholar 

  44. Gu, L. C. et al. Metabolic coupling of dehydration and decarboxylation in the curacin A pathway: functional identification of a mechanistically diverse enzyme pair. J. Am. Chem. Soc. 128, 9014–9015 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Calderone, C. T., Kowtoniuk, W. E., Kelleher, N. L., Walsh, C. T. & Dorrestein, P. C. Convergence of isoprene and polyketide biosynthetic machinery: isoprenyl-S-carrier proteins in the pksX pathway of Bacillus subtilis. Proc. Natl Acad. Sci. USA 103, 8977–8982 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Calderone, C. T. Isoprenoid-like alkylations in polyketide biosynthesis. Nat. Prod. Rep. 25, 845–853 (2008).

    Article  CAS  PubMed  Google Scholar 

  47. Rahman, A. S., Hothersall, J., Crosby, J., Simpson, T. J. & Thomas, C. M. Tandemly duplicated acyl carrier proteins, which increase polyketide antibiotic production, can apparently function either in parallel or in series. J. Biol. Chem. 280, 6399–6408 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Cooper, S. M. et al. Shift to pseudomonic acid B production in P. fluorescens NCIMB10586 by mutation of mupirocin tailoring genes mupO, mupU, mupV, and macpE. Chem. Biol. 12, 825–833 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Hothersall, J. et al. Mutational analysis reveals that all tailoring region genes are required for production of polyketide antibiotic mupirocin by Pseudomonas fluorescens: pseudomonic acid B biosynthesis precedes pseudomonic acid A. J. Biol. Chem. 282, 15451–15461 (2007). A comprehensive demonstration of the need for all genes in the mup cluster, and analysis by double gene knockouts to check the order in which gene products work.

    Article  CAS  PubMed  Google Scholar 

  50. Mantle, P. G., De Langen, M. & Teo, V. K. Differentiating the biosynthesis of pseudomonic acids A and B. J. Antibiot. 54, 166–174 (2001).

    Article  CAS  Google Scholar 

  51. Chen, X. H. et al. Structural and functional characterization of three polyketide synthase gene clusters in Bacillus amyloliquefaciens FZB 42. J. Bacteriol. 188, 4024–4036 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. El-Sayed, A. K., Hothersall, J. & Thomas, C. M. Quorum-sensing-dependent regulation of biosynthesis of the polyketide antibiotic mupirocin in Pseudomonas fluorescens NCIMB 10586. Microbiology 147, 2127–2139 (2001). A study of the regulation of mupirocin production that also provides a practical mechanism for controlling and boosting production of the antibiotic.

    Article  CAS  PubMed  Google Scholar 

  53. Wei, H. L. & Zhang, L. Q. Quorum-sensing system influences root colonization and biological control ability in Pseudomonas fluorescens 2P24. Antonie Van Leeuwenhoek 89, 267–280 (2006).

    Article  PubMed  Google Scholar 

  54. Broom, N. J. P. et al. The chemistry of pseudomonic acid.17. Dual-action C-1 oxazole derivatives of pseudomonic acid having an extended spectrum of antibacterial activity. J. Med. Chem. 39, 3596–3600 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Brown, P. et al. The chemistry of pseudomonic acid.18. Heterocyclic replacement of the α,β-unsaturated ester: synthesis, molecular modeling, and antibacterial activity. J. Med. Chem. 40, 2563–2570 (1997).

    Article  CAS  PubMed  Google Scholar 

  56. Bennett, I. et al. Synthesis and antibacterial properties of β-diketone acrylate bioisosteres of pseudomonic acid A. Bioorg. Med. Chem. Lett. 9, 1847–1852 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Class, Y. J. & Deshong, P. The pseudomonic acids. Chem. Rev. 95, 1843–1857 (1995).

    Article  CAS  Google Scholar 

  58. Kozikowski, A. P., Schmiesing, R. J. & Sorgi, K. L. The conversion of methyl pseudomonate-C to pseudomonic acid-A. Tetrahedron Lett. 22, 059–2062 (1981).

    Article  Google Scholar 

  59. Balog, A., Yu, M. S. & Curran, D. P. A practical asymmetric synthesis of a pseudomonic acid precursor from D-arabinose or D-xylose. Synth. Commun. 26, 935–944 (1996).

    Article  Google Scholar 

  60. Khan, N., Xiao, H. Y., Zhang, B., Cheng, X. H. & Mootoo, D. R. Oxocarbenium ion cyclisations under non-acidic conditions: synthesis of tetrahydropyran analogues of the pseudomonic acids. Tetrahedron 55, 8303–8312 (1999).

    Article  CAS  Google Scholar 

  61. Sugawara, K., Imanishi, Y. & Hashiyama, T. Efficient and practical synthesis of both enantiomers of 6-silyloxy-3-pyranone derivatives. Tetrahedron Asymmetry 11, 4529–4535 (2000).

    Article  CAS  Google Scholar 

  62. Honda, T. & Kimura, N. Enantioselection deprotonation of meso-cycloheptanone derivative: application to the synthesis of a potential intermediate for pseudomonic acid B. Org. Lett. 4, 4567–4570 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. McKay, C., Simpson, T. J., Willis, C. L., Forrest, A. K. & O'Hanlon, P. J. A versatile approach to the total synthesis of the pseudomonic acids. Chem. Commun. (Camb.) 2000, 1109–1110 (2000).

    Article  Google Scholar 

  64. Marko, I. E. & Plancher, J. M. Novel tandem “ene-ISMS” methodology. Efficient and versatile assembly of a pseudomonic acid C analogue. Tetrahedron Lett. 40, 5259–5262 (1999).

    Article  CAS  Google Scholar 

  65. van Innis, L., Plancher, J. M. & Marko, I. E. Stereoselective synthesis of methyl monate C. Org. Lett. 8, 6111–6114 (2006).

    Article  CAS  PubMed  Google Scholar 

  66. Critchley, I. A. & Ochsner, U. A. Recent advances in the preclinical evaluation of the topical antibacterial agent REP8839. Curr. Opin. Chem. Biol. 12, 409–417 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Zhou, H., Xie, X. K. & Tang, Y. Engineering natural products using combinatorial biosynthesis and biocatalysis. Curr. Opin. Biotechnol. 19, 590–596 (2008).

    Article  CAS  PubMed  Google Scholar 

  68. Shiozawa, H. et al. Thiomarinol-B and thiomarinol-C, new antimicrobial antibiotics produced by a marine bacterium. J. Antibiot. 48, 907–909 (1995). A description of a very important group of natural products that are related to the pseudomonic acids.

    Article  CAS  Google Scholar 

  69. Oliva, B., O'Neill, A., Wilson, J. M., O'Hanlon, P. J. & Chopra, I. Antimicrobial properties and mode of action of the pyrrothine holomycin. Antimicrob. Agents Chemother. 45, 532–539 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Marion, O., Gao, X., Marcus, S. & Hall, D. G. Synthesis and preliminary evaluation of simplified thiomarinol analogs. Bioorg. Med. Chem. 17, 1006–1017 (2009).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Current work on mupirocin in the authors' laboratories is supported by grant BB/E021611/1, which is jointly funded by the Biotechnology and Biological Sciences Research Council and the Engineering and Physical Sciences Research Council.

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Authors and Affiliations

  1. School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Christopher M. Thomas & Joanne Hothersall

  2. School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK

    Christine L. Willis & Thomas J. Simpson

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DATABASES

Entrez Genome Project

Bacillus amyloliquefaciens

Escherichia coli

Methanothermobacter thermautotrophicus

Pseudomonas fluorescens

Salmonella enterica subsp. enterica serovar Typhimurium

Staphylococcus aureus

Streptomyces clavuligerus

Vibrio fischeri

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Glossary

Isoleucyl-tRNA synthetase

The enzyme responsible for the addition of isoleucine to tRNAIle, using the energy from ATP to drive the reaction.

Rossman fold

A structural motif found in proteins that bind nucleotides. It is composed of three or more parallel β-strands linked to and alternating with two α-helices.

Stringent response

A reaction to amino acid starvation that is found in all prokaryotes and that prevents the wasteful biosynthesis of gene expression machinery. Guanosine pentaphosphate and guanosine tetraphosphate are produced by the ribosomal proteins GTP pyrophosphokinase (RelA) and L11A when there are no charged tRNAs available to bind to the ribosome, and this is converted to a signal that reduces the synthesis of ribosomal and RNA polymerase components.

Methicillin-resistant S. aureus

Specific strains of S. aureus that have acquired a mutation in penicillin-binding protein 2 (PBP2), rendering them resistant to methicillin, along with having resistance to many other β-lactam antibiotics and other commonly used antibiotics owing to gene transfer from plasmids and transposable elements.

Polyketide

A compound that is synthesized by the successive decarboxylative condensation of extender units such as malonate and methylmalonate onto organic acid starter units such as acetate to formally create a polymer with keto groups on alternate backbone carbons.

Polyketide synthase

An enzyme that is responsible for polyketide synthesis and has, at a minimum, ketosynthase and acyl carrier protein functions that carry the starter and extender units, respectively. Type I polyketide synthases incorporate these functions into a single polypeptide and have one ketosynthase and one acyl carrier protein for each condensation, whereas type II enzymes consist of multiple unifunctional polypeptides that catalyse multiple rounds of condensation.

Quorum sensing

A mechanism of regulating gene expression in response to cell density per unit volume, normally involving a diffusible signal that is produced constitutively by the cells and to which the cells respond when the concentration rises above a certain threshold.

Ene-ISMS reaction

A reaction involving an unsaturated double carbon bond followed by a concomitant intramolecular silyl-mediated Sakurai (ISMS) cyclization.

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Thomas, C., Hothersall, J., Willis, C. et al. Resistance to and synthesis of the antibiotic mupirocin. Nat Rev Microbiol 8, 281–289 (2010). https://doi.org/10.1038/nrmicro2278

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