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    Phenotypic variation

    Within clonal bacterial populations not all cells exhibit the same phenotype, even though they grow in the same environment (see some of our old but still relevant reviews on this topic here (Smits et al., Nat. Rev. Microbiol. 2006) and here (Veening et al., Ann. Rev. Microbiol. 2008)). The molecular sources contributing to phenotypic variation are diverse and can originate from noise in gene expression (Bhogale et al., NAR 2014) to heterogeneity in growth rates or cell cycle state. Phenotypic variation helps pathogenic bacteria to elude the host immune response or resist antibiotic pressure. How heterogeneity contributes to infection outcome is poorly understood. The role of phenotypic variation on antibiotic resistance development is also unclear but certainly plays a role (Sorg and Veening, Nat. commun. 2015).

    Using single cell analysis and orthogonal gene regulatory networks we aim to identify the molecular mechanisms underlying phenotypic variation and the importance of this cell-to-cell variability in pneumococcal pathogenesis.