S.aureus LTA suppressors
Increased c-di-AMP levels allow Staphylococcus aureus growth                 in the absence of lipoteichoic acid
The cell wall polymer lipoteichoic acid (LTA) is crucial for normal                 growth of many Gram-positive bacteria. Inactivation of LtaS, the enzyme responsible                 for LTA synthesis in Staphylococcus aureus can be achieved but only under                 high-osmolarity conditions. In this work, LTA-deficient S. aureus suppressor strains                 that regained the ability to grow almost normally in the absence of LTA were                 characterized. Using a whole genome sequencing approach compensatory mutations were                 identified and revealed that mutations within gdpP (GGDEF domain protein containing                 phosphodiesterase) allow laboratory and clinical isolates of S. aureus to grow in                 the absence of LTA. GdpP has phosphodiesterase activity in vitro and uses c-di-AMP                 as a substrate. We further demonstrate that GdpP also functions in vivo as                 c-di-AMP-specific phosphodiesterase, as intracellular c-di-AMP levels increase                 drastically upon its deletion. We quantify for the first time c-di-AMP levels in the                 cytoplasm of a bacterium and characterize S. aureus proteins involved in its                 synthesis and degradation. Furthermore, our findings suggest a link between this                 novel secondary messenger and cell wall properties in Gram-positive                 bacteria.