A bacterial toxin-antitoxin system involved in an unusual response to genotoxic stress

To contend with environmental challenges, bacteria have evolved numerous stress response pathways. A notable example is the adoption of a dormant state called persistence, whereby cells reversibly restrict their growth and await favorable conditions. The genetics of persistence remain poorly understood, and genes called toxin-antitoxin (TA) systems have controversially been implicated in this phenotype. To examine their role in persistence, we construct a pan-TA deletion strain of the bacterial pathogen Legionella pneumophila and test its capacity to survive diverse stresses. We identify a single predicted TA system, GndRX, that under genotoxic stress conditions leads to cell death rather than promoting survival, whereas ∆gndRX cells adopt a viable but nonculturable state. Strikingly, this enhanced survival is conferred to wild-type cells in a contact-dependent manner during co-culture. Despite having homology to other TA systems, GndRX displays non-canonical activity, and we hypothesize that it has undergone functional domestication by the cell. Overall, our work reveals both a new physiological function for TA systems in bacteria as well as a heretofore undescribed phenomenon of contact-dependent survival within persister cells.