Figure 2. Persisters at systemic sites are a reservoir for plasmid transfer in the gut.

a) Working hypothesis. Same as Fig. 1a, but donors are introduced by intravenous infection. b) I.V. infection mouse model. c) Persisters in the spleens and livers. In two independent experiments, n=8 mice (grey circles) were infected i.v. with an equal mix of five SL1344 P2^{cat TAG} strains (Sm^R, Cm^R). Black circles indicate control mice (n=8) infected for 5 days without ceftriaxone treatment. Extended Data Fig. 5a shows counts for additional organs. d-e) SPI-2 promotes donor reservoir formation at systemic sites. In two independent experiments, mice were infected as described in panel B with donors, i.e. mixtures of five wild-type (n=6; closed circles) or SPI-2 deficient (n=6; open circles) SL1344 P2^{cat TAG} strains (Sm^R, Cm^R). d) Donor populations in internal organs from mice infected with wild-type (solid blue) or SPI-2 deficient donors (open blue). Lines indicate the median. e) Fecal populations from mice from panel d. Transconjugant proportions in feces from experiments with wild-type (solid black circles; grey bars indicate median) or noninvasive donors (open black circles; white bars indicate median). Dashed lines connect data points from the same mice. Statistics are performed using a two-tailed Mann-Whitney U test (p>0.05 (ns), p<0.05 (*), p<0.01 (**), p<0.001 (***)). Dotted lines: detection limits.