Journal
PHARMACEUTICALS
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ph11010014
Keywords
persistence; tolerance; metabolism; biofilms; next-generation sequencing
Categories
Funding
- COBRE Center for Computational Biology of Human Disease [NIH P20 GM109035]
- National Science Foundation Graduate Research Fellowship [1644760]
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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.
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