Tuesday, November 15, 2016
1:00 pm, MRB 202 Conference Room
Dr. William Mather
Department of Physics, Virginia Tech
Excitable toxin-antitoxin modules coordinated through intracellular bottlenecks
Chronic infections present a serious threat to the health of humans by decreasing life expectancy and quality. They have more recently been attributed to the existence of persister cells within bacterial populations which constitute a small fraction of the population capable of surviving a wide range of environmental stressors including starvation, DNA damage, and heat shock. Persistence also allows the survival of successive applications of antibiotics resulting in chronic infections. Persistence has been strongly linked to toxin-antitoxin (TA) modules, operons with an evolutionarily conserved motif including a toxin that halts cell growth and an antitoxin that under healthy conditions neutralizes the toxin, typically by forming a complex which protects the antitoxin from rapid proteolytic degradation and performs some regulatory action on the operon. While many such modules have been identified and studied in a wide range of organisms, little consideration of interactions between multiple modules within a single host has been made. Moreover, the multitude of different antitoxin species share a limited number of proteolytic pathways, strongly suggesting competition between antitoxins for degradation machinery. Here we present a theoretical understanding of the dynamics of multiple TA modules whose activity is coupled through either proteolytic activity, a toxic effect on cell growth rate, or both. We also present theoretical mechanisms by which the persistent state is potentially tunable by regulation of proteolysis. Such regulation or indirect coordination between multiple TA modules may be at the heart of bacterial robustness owed to persistence.