The magnitude of heterogeneity in individual-cell growth dynamics is an inherent characteristic of Salmonella enterica ser. Typhimurium strains.

Individual-cell heterogeneity is a major source of variability in biological systems affecting importantly, among others, microbial behavior. Characterization of cell populations of pathogenic bacterial strains in their entirety, ignoring the phenotypic variability of single cells, may result in erroneous safety risk estimates. The objective of the present study was the evaluation and comparison of the heterogeneity in the individual-cell growth dynamics of different strains of Salmonella enterica. The stochasticity in the growth of single cells of five S. enterica ser. Typhimurium strains was quantitatively described using time-lapse microscopy, and the existence of a strain effect was statistically assessed. In total, 831 growing microcolonies originating from single cells were monitored and analyzed, and the growth kinetic parameters of lag time (λ) and maximum specific growth rate (μ _max ) for each one of them were estimated. An extensive heterogeneity in individual-cell growth kinetics was recorded, while significant inter-strain differences in their heterogeneity were evident based on simultaneous Bonferroni confidence intervals and Levene's tests. The Logistic and LogLogistic probability distribution provided the best fitting for μ _max and λ data, respectively for all the tested strains. The strain effect on the above distributions was also demonstrated with pairwise comparisons of the decile differences. The impact of strain-dependent heterogeneity on microbial growth was visualized by comparing stochastic growth curves of different strains using Monte Carlo simulation. In conclusion, the individual-cell growth dynamics of S. enterica are heterogeneous, with the magnitude of the observed heterogeneity appearing to be an inherent characteristic of bacterial strains.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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