Quantification of within patient Staphylococcus aureus phenotypic heterogeneity as a proxy for presence of persisters across clinical presentations

This dataset is described in the Supplementary Material of the paper (Suppl. Method S8) The small proportion of rifampicin resistant mutants arising from the clonal rifampicin susceptible populations founding our in vitro biofilms demonstrates that genetic diversification occurs during the experiment. To rule out that genetic diversity underlies the heterogeneous phenotypes observed, we performed a small proof-of principle-experiment. It consisted in picking a set of ten colonies (representative of the range of colony sizes observed after 48 h of incubation) and sequence their whole-genome. We did this four times: for two conditions (RIF and RIF+LVX) and with two clinical isolates (CI1379, CI1564). The picked colonies are indicated on Suppl. Fig. S6A. All had very similar radial growth rates but different appearance times (Suppl. Fig. S6B, C, D). We found that out of the 40 colonies, five harboured mutations differentiating them from other colonies of the corresponding isolate (Suppl. Fig. S6E). These mutations were not systematically harboured by colonies with the latest appearance time, and they did not affect proteins playing a key role in stress response.