Figure 3.

Bacterial PTS-Crp Signaling Regulates Metformin Effects on Host Metabolism and Lifespan

(A) Diagram of the PTS-Crp signaling pathway in E. coli.

(B–D) Glucose supplementation (B); deletion of E. coli OP50 pts H, I, and crr (C); and cyaA (D) abolishes worm lifespan extension by metformin.

(E) Metformin upregulates Crp expression in control E. coli OP50 but not in OP50 Δcrp or ΔcyaA mutants or with glucose supplementation. Significance stars represent metformin effect (purple) and metformin-genotype or nutrient interaction (green).

(F) Dose-dependent upregulation of Crp in E. coli OP50 extends the worm lifespan.

(G) Overexpression of Crp in E. coli OP50 upregulates Pacs-2::GFP expression in worms. Each panel shows 5 individual worms.

(H) Effect of overexpression of E. coli Crp on the worm lifespan is dependent on bacterial cyaA.

(I and J) Metformin extends the lifespan in flies grown on chemically defined medium with E. coli OP50 (I) but not with an OP50 Δcrp mutant (J).

(K) E. coli OP50 overexpressing Crp extends the fly lifespan on chemically defined medium.

Data are represented as mean ± SEM. n.s., non-significant; ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗p < 0.001.

See also Table S1 for lifespan statistics.