Antitoxin ? Reverses Toxin ?-Facilitated Ampicillin Dormants.

ABSTRACT: Toxin-antitoxin (TA) modules are ubiquitous in bacteria, but their biological importance in stress adaptation remains a matter of debate. The inactive ?-?₂-? TA complex is composed of one labile ?₂ antitoxin dimer flanked by two stable ? toxin monomers. Free toxin ? reduces the ATP and GTP levels, increases the (p)ppGpp and c-di-AMP pool, inactivates a fraction of uridine diphosphate-N-acetylglucosamine, and induces reversible dormancy. A small subpopulation, however, survives toxin action. Here, employing a genetic orthogonal control of ? and ? levels, the fate of bacteriophage SPP1 infection was analyzed. Toxin ? induces an active slow-growth state that halts SPP1 amplification, but it re-starts after antitoxin expression rather than promoting abortive infection. Toxin ?-induced and toxin-facilitated ampicillin (Amp) dormants have been revisited. Transient toxin ? expression causes a metabolic heterogeneity that induces toxin and Amp dormancy over a long window of time rather than cell persistence. Antitoxin ? expression, by reversing ? activities, facilitates the exit of Amp-induced dormancy both in rec⁺ and recA cells. Our findings argue that an unexploited target to fight against antibiotic persistence is to disrupt toxin-antitoxin interactions.

SUBMITTER: Moreno-Del Alamo M 

PROVIDER: S-EPMC7765365 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature