Molecular mechanisms of antibiotic resistance revisited

doi:10.1038/s41579-022-00820-y

Review

. 2023 May;21(5):280-295.

doi: 10.1038/s41579-022-00820-y. Epub 2022 Nov 21.

Molecular mechanisms of antibiotic resistance revisited

Elizabeth M Darby¹, Eleftheria Trampari², Pauline Siasat¹, Maria Solsona Gaya², Ilyas Alav¹, Mark A Webber^{3

4}, Jessica M A Blair⁵

Affiliations

¹ College of Medical and Dental Sciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
² Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.
³ Quadram Institute Bioscience, Norwich Research Park, Norwich, UK. Mark.Webber@quadram.ac.uk.
⁴ Medical School, University of East Anglia, Norwich Research Park, Norwich, UK. Mark.Webber@quadram.ac.uk.
⁵ College of Medical and Dental Sciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK. J.M.A.Blair@bham.ac.uk.

PMID: 36411397
DOI: 10.1038/s41579-022-00820-y

Review

Molecular mechanisms of antibiotic resistance revisited

Elizabeth M Darby et al. Nat Rev Microbiol. 2023 May.

. 2023 May;21(5):280-295.

doi: 10.1038/s41579-022-00820-y. Epub 2022 Nov 21.

Authors

Elizabeth M Darby¹, Eleftheria Trampari², Pauline Siasat¹, Maria Solsona Gaya², Ilyas Alav¹, Mark A Webber^{3

4}, Jessica M A Blair⁵

Affiliations

¹ College of Medical and Dental Sciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK.
² Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.
³ Quadram Institute Bioscience, Norwich Research Park, Norwich, UK. Mark.Webber@quadram.ac.uk.
⁴ Medical School, University of East Anglia, Norwich Research Park, Norwich, UK. Mark.Webber@quadram.ac.uk.
⁵ College of Medical and Dental Sciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK. J.M.A.Blair@bham.ac.uk.

PMID: 36411397
DOI: 10.1038/s41579-022-00820-y

Erratum in

Author Correction: Molecular mechanisms of antibiotic resistance revisited.
Darby EM, Trampari E, Siasat P, Gaya MS, Alav I, Webber MA, Blair JMA. Darby EM, et al. Nat Rev Microbiol. 2024 Apr;22(4):255. doi: 10.1038/s41579-024-01014-4. Nat Rev Microbiol. 2024. PMID: 38308008 No abstract available.

Abstract

Antibiotic resistance is a global health emergency, with resistance detected to all antibiotics currently in clinical use and only a few novel drugs in the pipeline. Understanding the molecular mechanisms that bacteria use to resist the action of antimicrobials is critical to recognize global patterns of resistance and to improve the use of current drugs, as well as for the design of new drugs less susceptible to resistance development and novel strategies to combat resistance. In this Review, we explore recent advances in understanding how resistance genes contribute to the biology of the host, new structural details of relevant molecular events underpinning resistance, the identification of new resistance gene families and the interactions between different resistance mechanisms. Finally, we discuss how we can use this information to develop the next generation of antimicrobial therapies.

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References

1. Blair, J. M. A., Webber, M. A., Baylay, A. J., Ogbolu, D. O. & Piddock, L. J. V. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 13, 42–51 (2015). - PubMed - DOI
1. Whittle, E. E. et al. Efflux impacts intracellular accumulation only in actively growing bacterial cells. mBio 12, e0260821 (2021). - PubMed - DOI
1. Alav, I. et al. Structure, assembly, and function of tripartite efflux and type 1 secretion systems in gram-negative bacteria. Chem. Rev. 121, 5479–5596 (2021). - PubMed - PMC - DOI
1. Klenotic, P. A., Morgan, C. E. & Yu, E. W. Cryo-EM as a tool to study bacterial efflux systems and the membrane proteome. Fac. Rev. 10, 24 (2021). - PubMed - PMC - DOI
1. Malaka De Silva, P. et al. A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella. Proc. Biol. Sci. 289, 20220581 (2022). - PubMed - PMC

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[1] Blair, J. M. A., Webber, M. A., Baylay, A. J., Ogbolu, D. O. & Piddock, L. J. V. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 13, 42–51 (2015). - PubMed - DOI

[2] Blair, J. M. A., Webber, M. A., Baylay, A. J., Ogbolu, D. O. & Piddock, L. J. V. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 13, 42–51 (2015). - PubMed - DOI

[3] Whittle, E. E. et al. Efflux impacts intracellular accumulation only in actively growing bacterial cells. mBio 12, e0260821 (2021). - PubMed - DOI

[4] Whittle, E. E. et al. Efflux impacts intracellular accumulation only in actively growing bacterial cells. mBio 12, e0260821 (2021). - PubMed - DOI

[5] Alav, I. et al. Structure, assembly, and function of tripartite efflux and type 1 secretion systems in gram-negative bacteria. Chem. Rev. 121, 5479–5596 (2021). - PubMed - PMC - DOI

[6] Alav, I. et al. Structure, assembly, and function of tripartite efflux and type 1 secretion systems in gram-negative bacteria. Chem. Rev. 121, 5479–5596 (2021). - PubMed - PMC - DOI

[7] Klenotic, P. A., Morgan, C. E. & Yu, E. W. Cryo-EM as a tool to study bacterial efflux systems and the membrane proteome. Fac. Rev. 10, 24 (2021). - PubMed - PMC - DOI

[8] Klenotic, P. A., Morgan, C. E. & Yu, E. W. Cryo-EM as a tool to study bacterial efflux systems and the membrane proteome. Fac. Rev. 10, 24 (2021). - PubMed - PMC - DOI

[9] Malaka De Silva, P. et al. A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella. Proc. Biol. Sci. 289, 20220581 (2022). - PubMed - PMC

[10] Malaka De Silva, P. et al. A tale of two plasmids: contributions of plasmid associated phenotypes to epidemiological success among Shigella. Proc. Biol. Sci. 289, 20220581 (2022). - PubMed - PMC

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Molecular mechanisms of antibiotic resistance revisited

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