In this section
@article{Corrigan:2015:10.1074/jbc.M114.598300,
author = {Corrigan, RM and Bowman, L and Willis, AR and Kaever, V and Gruendling, A},
doi = {10.1074/jbc.M114.598300},
journal = {Journal of Biological Chemistry},
pages = {5826--5839},
title = {Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus},
url = {http://dx.doi.org/10.1074/jbc.M114.598300},
volume = {290},
year = {2015}
}
TY - JOUR
AB - Nucleotide-signaling pathways are found in all kingdoms oflife and are utilized to coordinate a rapid response to externalstimuli. The stringent response alarmones guanosine tetra(ppGpp)and pentaphosphate (pppGpp) control a globalresponse allowing cells to adapt to starvation conditions such asamino acid depletion. One more recently discovered signalingnucleotide is the secondary messenger cyclic diadenosinemonophosphate (c-di-AMP). Here, we demonstrate that thissignaling nucleotide is essential for the growth of Staphylococcusaureus, and its increased production during late growthphases indicates that c-di-AMP controls processes that areimportant for the survival of cells in stationary phase. By examiningthe transcriptional profile of cells with high levels of c-diAMP,we reveal a significant overlap with a stringent responsetranscription signature. Examination of the intracellular nucleotidelevels under stress conditions provides further evidencethat high levels of c-di-AMP lead to an activation of the stringentresponse through a RelA/SpoT homologue (RSH) enzymedependentincrease in the (p)ppGpp levels. This activation isshown to be indirect as c-di-AMP does not interact directly withthe RSH protein. Our data extend this interconnection furtherby showing that the S. aureus c-di-AMP phosphodiesteraseenzyme GdpP is inhibited in a dose-dependent manner byppGpp, which itself is not a substrate for this enzyme. Altogether,these findings add a new layer of complexity to ourunderstanding of nucleotide signaling in bacteria as they highlightintricate interconnections between different nucleotidesignalingnetworks.
AU - Corrigan,RM
AU - Bowman,L
AU - Willis,AR
AU - Kaever,V
AU - Gruendling,A
DO - 10.1074/jbc.M114.598300
EP - 5839
PY - 2015///
SN - 0021-9258
SP - 5826
TI - Cross-talk between Two Nucleotide-signaling Pathways in Staphylococcus aureus
T2 - Journal of Biological Chemistry
UR - http://dx.doi.org/10.1074/jbc.M114.598300
UR - http://hdl.handle.net/10044/1/55959
VL - 290
ER -
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