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Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions

Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceuticals 2018, 11(1), 14;
Received: 23 December 2017 / Revised: 25 January 2018 / Accepted: 27 January 2018 / Published: 1 February 2018
Persistence is a phenomenon during which a small fraction of a total bacterial population survives treatment with high concentrations of antibiotics for an extended period of time. In conjunction with biofilms, antibiotic persisters represent a major cause of recalcitrant and recurring infections, resulting in significant morbidity and mortality. In this review, we discuss the clinical significance of persister cells and the central role of bacterial metabolism in their formation, specifically with respect to carbon catabolite repression, sugar metabolism, and growth regulation. Additionally, we will examine persister formation as an evolutionary strategy used to tolerate extended periods of stress and discuss some of the response mechanisms implicated in their formation. To date, the vast majority of the mechanistic research examining persistence has been conducted in artificial in vitro environments that are unlikely to be representative of host conditions. Throughout this review, we contextualize the existing body of literature by discussing how in vivo conditions may create ecological niches that facilitate the development of persistence. Lastly, we identify how the development of next-generation sequencing and other “big data” tools may enable researchers to examine persistence mechanisms within the host to expand our understanding of their clinical importance. View Full-Text
Keywords: persistence; tolerance; metabolism; biofilms; next-generation sequencing persistence; tolerance; metabolism; biofilms; next-generation sequencing
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Cabral, D.J.; Wurster, J.I.; Belenky, P. Antibiotic Persistence as a Metabolic Adaptation: Stress, Metabolism, the Host, and New Directions. Pharmaceuticals 2018, 11, 14.

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