Chromosomal toxin-antitoxin systems may act as anti-addiction modules

Laboratoire de Génétique et de Physiologie Bactérienne, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, 12 rue des Professeurs Jeener et Brachet, B : 6041 Gosselies, Belgium

^* To whom correspondence should be addressed. Email: lvmelder{at}ulb.ac.be.

	Abstract

Toxin-antitoxin (TA) systems are widespread among bacterial chromosomes and mobile genetic elements. Although in plasmids TA systems have a clear role in their vertical inheritance by selectively killing plasmid-free daughter-cells (post-segregational killing or addiction phenomenon), the physiological role of chromosomally-encoded ones still remains under debate. The assumption that chromosomally-encoded TA systems are part of stress response networks and/or programmed cell death machinery has been questioned recently by the observation that none of the 5 canonical chromosomally-encoded TA systems in the E. coli chromosome seems to confer any selective advantage under stressful conditions (Tsilibaris et al., J. Bacteriol., 2007). Their prevalence in bacterial chromosomes indicates that they might have been acquired through horizontal gene transfer. Once integrated in chromosomes, they might in turn interfere with their homologues encoded by mobile genetic elements. In this work, we show that the chromosomally-encoded ccd_Ech system indeed protects the cell against post-segregational killing mediated by its F-plasmid ccd_Fhomologue. Moreover, competition experiments have shown that this system confers a fitness advantage under post-segregational condition mediated by the ccd_F system. We propose that ccd_Ech acts as an anti-addiction module and, more generally, that the integration of TA systems in bacterial chromosomes could drive the evolution of plasmid-encoded ones and select toxins that are no longer recognised by the anti-addiction module.