“Gene accordions” cause genotypic and phenotypic heterogeneity in clonal populations of Staphylococcus aureus

Gene tandem amplifications are thought to drive bacterial evolution, but they are transient in the absence of selection, making their investigation challenging. Here, we analyze genomic sequences of Staphylococcus aureus USA300 isolates from the same geographical area to identify variations in gene copy number, which we confirm by long-read sequencing. We find several hotspots of variation, including the csa1 cluster encoding lipoproteins known to be immunogenic. We also show that the csa1 locus expands and contracts during bacterial growth in vitro and during systemic infection of mice, and recombination creates rapid heterogeneity in initially clonal cultures. Furthermore, csa1 copy number variants differ in their immunostimulatory capacity, revealing a mechanism by which gene copy number variation can modulate the host immune response.


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All studies must disclose on these points even when the disclosure is negative. Sample sizes used in evolutionary experiments (Fig 2 and Fig 4) were based on the feasibility of the experimental workload. 6 parallel cultures ensured sufficient biological replication and 16 Clones screened at each day allowed sufficient to describe variation Number of mice used for in vivo experiments were used in line with our allowance of animal numbers per group. Binding us to 6 mice per group. This is in our eyes sufficient to determine variation between individual mice.
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