Figure 1. Intracellular phenotype switching to SCV and immune evasion of S. aureus.

1. Different routes to SCV formation. Stable SCVs are caused by a variety of mutations in certain bacterial genes leading to auxotrophy (upper panel). Phenotype switching without mutations predominantly results in unstable SCVs during intracellular growth as shown in the Tuchscherr study. SCVs display reduced virulence and altered antibiotic sensitivity; unstable SCVs arising from phenotype switching can rapidly revert to the wild type form with increased virulence and rapid growth (lower panel).
2. Possible outcomes after intracellular S. aureus infection. After internalization into the host cell, not all bacteria undergo phenotype switching. S. aureus can be cleared, it can cause cell death or it can undergo a phenotype switch and cause a persistent infection. The phenotype switch to SCVs allows S. aureus to evade the immune response and leads to the formation of a viable reservoir of bacteria from which the bacteria can escape and disseminate or re-infect the host.