FIG 6.

Inoculum size strongly influences pathogen burden. Mice were infected with different inocula of V. cholerae and sacrificed at 24 h to isolate bacteria. (A) The V. cholerae CFU number (black dots) and N_B (red triangles) were determined in the small intestine. Each data point represents one mouse (93 total). CFU (black line) and N_B (red line) were predicted by a mathematical model fitted to experimental data of mice infected with an intermediate inoculum of 1.48 × 10⁵ CFU V. cholerae per mouse (see Fig. 2). The blue curve shows the bacterial burden calculated by a Hill function of the inoculum size, N(t) = K × N(0)e^rt/[K+N(0)(e^rt − 1)] and K  =  a × N(0)/[b+N(0)] and was fitted to the logarithm of the experimental data using the Levenberg-Marquardt algorithm. The resulting values for the coefficients and the 95% confidence intervals are a = 9.244 (8.312, 10.18) and b = 1.227 (0.7051, 1.75) (adjusted R² = 0.8613). Dotted vertical lines represent model-fitted doses of 1.37 × 10³ and 1.48 × 10⁵ CFU. (B) Zoom-in of the predicted CFU numbers. The same data as the black line in panel A but on an enlarged, linear y axis to show the nonlinear relationship between the inoculum size and the bacterial load at 24 h more clearly. (C) Schematic representation of logistic growth and the dependence of the bacterial load modeled at a given time on the inoculum (10⁵, cyan; 10⁴, orange; 10³, green). (D) Differences between individual parameters (replication rates, death rates, and the log₁₀ of the carrying capacity) derived from our model fit of the high-inoculum experiments (Fig. 2) to the parameters derived from the low inoculum experiment fits (Fig. S3). The dotted line is set to zero for reference.