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Modern medicine is founded on the widespread use of broad spectrum antibacterials, both as effective treatments to life-threatening infections as well as prophylactic agents to prevent infections resulting from a range of medical procedures ranging from elective surgeries to organ transplantation. Despite this tremendous impact on human health, several factors threaten the long-term viability of these agents including the rise of multidrug resistance and emerging data linking antibiotic-induced disturbance of the microbiome to a variety of life-threatening and chronic diseases such as cancer and auto-immune disorders.The discovery of novel narrow spectrum antibacterials may address these concerns, since these agents would not suffer from pre-existing resistance mechanisms and the selective eradication of pathogenic bacteria would serve to limit the impact on the beneficial organisms in the microbiota. This review outlines the progress achieved to date in identifying narrow spectrum antibacterials from both traditional natural product sources and synthetic/target-based drug discovery approaches and highlights emerging technologies that offer promise for the future.

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