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Targeting virulence: a new paradigm for antimicrobial therapy

Abstract

Clinically significant antibiotic resistance has evolved against virtually every antibiotic deployed. Yet the development of new classes of antibiotics has lagged far behind our growing need for such drugs. Rather than focusing on therapeutics that target in vitro viability, much like conventional antibiotics, an alternative approach is to target functions essential for infection, such as virulence factors required to cause host damage and disease. This approach has several potential advantages including expanding the repertoire of bacterial targets, preserving the host endogenous microbiome, and exerting less selective pressure, which may result in decreased resistance. We review new approaches to targeting virulence, discuss their advantages and disadvantages, and propose that in addition to targeting virulence, new antimicrobial development strategies should be expanded to include targeting bacterial gene functions that are essential for in vivo viability. We highlight both new advances in identifying these functions and prospects for antimicrobial discovery targeting this unexploited area.

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Figure 1: Timeline of antibiotic deployment and the evolution of antibiotic resistance.
Figure 2: Traditional targets of antibacterial compounds.
Figure 3: Bacterial protein functions that can be targeted to inhibit virulence and examples of virulence inhibitors.

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Acknowledgements

We thank E.J. Rubin, J.E. Gomez and S.A. Stanley for helpful discussions and critical reading of this manuscript and J.S.W. Lee for assistance in preparing figures.

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Correspondence to Deborah T Hung.

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Clatworthy, A., Pierson, E. & Hung, D. Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3, 541–548 (2007). https://doi.org/10.1038/nchembio.2007.24

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