Send to

Choose Destination
J Biol Chem. 2019 Sep 9. pii: jbc.RA119.010046. doi: 10.1074/jbc.RA119.010046. [Epub ahead of print]

c-di-AMP assists osmoadaptation by regulating the Listeria monocytogenespotassium transporters KimA and KtrCD.

Author information

General Microbiology, University of Göttingen, Germany.
University of Göttingen, Germany.
University of Maryland, United States.


Many bacteria and some archaea produce the second messenger cyclic diadenosine monophosphate (c-di-AMP). c-di-AMP controls the uptake of osmolytes in Firmicutes, including the human pathogen Listeria monocytogenes, making it essential for growth. c-di-AMP is known to directly regulate several potassium channels involved in osmolyte transport in species such as Bacillus subtilis and Streptococcus pneumoniae, but whether this same mechanism is involved in L. monocytogenes, or even whether similar ion channels were present, was not known. Here, we have identified and characterized the putative L. monocytogenes' potassium transporters KimA, KtrCD and KdpABC. We demonstrate that E. coli expressing KimA and KtrCD, but not KdpABC, transport potassium into the cell, and both KimA and KtrCD are inhibited by c-di-AMP in vivo. For KimA, c-di-AMP-dependent regulation requires the C-terminal domain. In vitro assays demonstrated the dinucleotide binds to the cytoplasmic regulatory subunit KtrC and to the KdpD sensor kinase of the KdpDE two-component system, which in Staphylococcus aureus regulates the corresponding KdpABC transporter. Finally, we also show that S. aureus contains a homolog of KimA, which mediates potassium transport. Thus, the c-di-AMP-dependent control of systems involved in potassium homeostasis seems to be conserved in phylogenetically related bacteria. Surprisingly, the growth of a L. monocytogenes mutant lacking the c-di-AMP synthesizing enzyme cdaAis only weakly inhibited by potassium. Thus, the physiological impact of the c-di-AMP-dependent control of potassium uptake seems to be less pronounced in L. monocytogenes than in other Firmicutes.


Escherichia coli (E. coli); cyclic diadenosine monophosphate (c-di-AMP); gram-positive bacteria; ion transport; osmoadaptation; osmotic swelling; regulation; second messenger; signal transduction; transporter

Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center