Preferential Use of Central Metabolism In Vivo Reveals a Nutritional Basis for Polymicrobial Infection
Figure 5
Polymicrobial infection alters central metabolism requirements for E. coli and P. mirabilis.
(A) Competitive indices (CI) were determined following co-challenge infections of female CBA/J mice with a 1∶1 ratio of wild-type: mutant bacteria for gnd (oxidative pentose phosphate pathway) and pckA (gluconeogenesis) for P. mirabilis at 48 hpi. Each dot represents bladder (closed symbols) and kidneys (open symbols) from an individual animal. Competitive indices (CI) were determined 48 hpi for mixed infections of (B) wild-type E. coli CFT073 and P. mirabilis HI4320 gnd, (C) wild-type HI4320 and CFT073 gnd, and (D) HI4320 gnd and CFT073 gnd mutant constructs. Each circle represents bladder or kidneys from an individual animal. In (A–D) bars indicate the median CI and significant differences in colonization (*) (P<0.05) were determined by Wilcoxon signed-rank test. (E) In vivo CI at 48 h and 7 d post-infection. (F) CI during logarithmic growth in LB medium. For (A–F) a CI<1 indicates a fitness defect. For mixed infections CFU/ml were determined following plating of serial dilutions on LB agar with and without tetracycline. CFU from tetracycline-containing plates (P. mirabilis are TetR) were subtracted from total CFU recovered on LB agar without antibiotics to determine CFU/ml for E. coli (TetS).