CAREER: Characterizing Persister Cell Metabolism in Bacteria

Antibiotic tolerance is one of the most critical global public health threats of the 21st century. Bacterial cells that are temporarily resistant to high levels of antibiotics are referred to as persisters. Nearly all bacterial cultures contain a small population of persister cells.

Persisters are thought to be responsible for recurring chronic infections and drug-resistant mutants. The goal of this project is to identify common mechanisms exhibited by persister cells from a variety of bacterial strains. Anti-persister strategies will developed based on our increased understanding of the underlying mechanisms.

Engagement of pre-college students in STEM activities is an emphasis of the outreach activities planned. Teaming is already underway with local elementary and middle schools with >80% underrepresented minority students. A summer workshop is planned, as well as development of short animations.

Articles describing the research results will be submitted to journals targeted at 4th-8th grade students such as Frontiers for Young Minds.

The persistence phenomenon has been documented across multiple microbes and in response to a variety of antibiotics. Persister cell survival is marked by growth inhibition during antibiotic treatment and resumption of growth upon removal of antibiotics. Persisters are generally assumed to be dormant cells with a depressed metabolism.

In contrast, hypothesis driving this project is that persisters have active but unique metabolic mechanisms that regulate the reversible switching and maintenance of these cells. An array of assays will be employed to understand how metabolism: (i) is involved in the formation of persister cells and (ii) maintains the survival and resuscitation of persister cells.

The results will challenge paradigms regarding persister cell dormancy and metabolism, shed light on persister cell resuscitation mechanisms, provide platforms for studying the metabolic heterogeneity of persister cell subpopulations during and after antibiotic treatment, and integrate multiple lines of evidence to enhance our understanding of the eco-evolutionary aspects of bacterial persistence.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.