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bioRxiv · 10.1101/754309

Staphylococcus aureus can survive in the absence of c-di-AMP upon inactivation of the main glutamine transporter

Zeden, M. S.·Kviatkovski, I.·Chittezham, V. T.·Fey, P. D.·Grundling, A.
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Abstract

A Staphylococcus aureus strain deleted for the c-di-AMP cyclase gene dacA is unable to survive in rich medium unless it acquires compensatory mutations. Previously identified mutations were in opuD, encoding the main glycine-betaine transporter, and alsT, encoding a predicted amino acid transporter. Here, we show that inactivation of OpuD restores the cell size of a dacA mutant to near wild-type size, while inactivation of AlsT does not, suggesting two different mechanisms for the growth rescue. AlsT was identified as an efficient glutamine transporter, indicating that preventing glutamine uptake in rich medium rescues the growth of the S. aureus dacA mutant. In addition, GltS was identified as a glutamine transporter. By performing growth curves with WT, alsT and gltS mutant strains in defined medium supplemented with ammonium, glutamine or glutamate, we revealed that ammonium and glutamine, but not glutamate promote the growth of S. aureus. This suggests that besides ammonium also glutamine can serve as a nitrogen source under these conditions. Ammonium and uptake of glutamine via AlsT inhibited c-di-AMP production, while glutamate uptake had no effect. These findings provide, besides the previously reported link between potassium and osmolyte uptake, a connection between nitrogen metabolism and c-di-AMP signalling in S. aureus. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/754309v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1f6f305org.highwire.dtl.DTLVardef@1cceafeorg.highwire.dtl.DTLVardef@57cba5org.highwire.dtl.DTLVardef@1fabed6_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Zeden, M. S., Kviatkovski, I., Chittezham, V. T., Fey, P. D., Grundling, A.. 2019-09-01. Staphylococcus aureus can survive in the absence of c-di-AMP upon inactivation of the main glutamine transporter. https://doi.org/10.1101/754309

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