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Molecular mechanisms that confer antibacterial drug resistance

Abstract

Antibiotics — compounds that are literally ‘against life’ — are typically antibacterial drugs, interfering with some structure or process that is essential to bacterial growth or survival without harm to the eukaryotic host harbouring the infecting bacteria. We live in an era when antibiotic resistance has spread at an alarming rate1,2,3,4 and when dire predictions concerning the lack of effective antibacterial drugs occur with increasing frequency. In this context it is apposite to ask a few simple questions about these life-saving molecules. What are antibiotics? Where do they come from? How do they work? Why do they stop being effective? How do we find new antibiotics? And can we slow down the development of antibiotic-resistant superbugs?

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Figure 1: Blockade of transpeptidation and transglycosylation steps of cell-wall biosynthesis by penicillins and vancomycins.
Figure 2: Structural and functional diversity of antibacterial drugs.
Figure 3: Principal resistance strategies for bacterial survival.
Figure 4: Counter-survival strategies.

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Acknowledgements

Experimental work cited in this review is supported by the National Institutes of Health. I thank R. Chen and I. Lessard for preparation of the artwork.

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Walsh, C. Molecular mechanisms that confer antibacterial drug resistance. Nature 406, 775–781 (2000). https://doi.org/10.1038/35021219

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