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Whole-organism phenotypic screening for anti-infectives promoting host health

Abstract

To date, antibiotics have been identified on the basis of their ability to kill bacteria or inhibit their growth rather than directly for their capacity to improve clinical outcomes of infected patients. Although historically successful, this approach has led to the development of an antibiotic armamentarium that suffers from a number of shortcomings, including the inevitable emergence of resistance and, in certain infections, suboptimal efficacy leading to long treatment durations, infection recurrence, or high mortality and morbidity rates despite apparent bacterial sterilization. Conventional antibiotics fail to address the complexities of in vivo bacterial physiology and virulence, as well as the role of the host underlying the complex, dynamic interactions that cause disease. New interventions are needed, aimed at host outcome rather than microbiological cure. Here we review the role of screening models for cellular and whole-organism infection, including worms, flies, zebrafish, and mice, to identify novel therapeutic strategies and discuss their future implications.

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Fig. 1: Conventional and nonconventional approaches to treating bacterial infection.
Fig. 2: Disease-tolerance curve analysis of parameters that affect host health.
Fig. 3: Small molecules with host-targeting activity and/or identified through whole-organism screening.

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We would like to acknowledge E. Office and S. Son for assistance with preparing the graphical abstract.

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Clatworthy, A.E., Romano, K.P. & Hung, D.T. Whole-organism phenotypic screening for anti-infectives promoting host health. Nat Chem Biol 14, 331–341 (2018). https://doi.org/10.1038/s41589-018-0018-3

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