Perspective of ions and messengers: an intricate link between potassium, glutamate, and cyclic di-AMP

Abstract

Potassium and glutamate are the most abundant ions in every living cell. Whereas potassium plays a major role to keep the cellular turgor and to buffer the negative charges of the nucleic acids, the major function of glutamate is to serve as the universal amino group donor. In addition, both ions are involved in osmoprotection in bacterial cells. Here, we discuss how bacterial cells maintain the homeostasis of both ions and how adaptive evolution allows them to live even at extreme potassium limitation. Interestingly, positively charged amino acids are able to partially replace potassium, likely by buffering the negative charge of DNA. A major factor involved in the control of potassium homeostasis in Gram-positive bacteria is the essential second messenger cyclic di-AMP. This nucleotide is synthesized in response to the potassium concentration and in turn controls the expression and activity of potassium transporters. We discuss the link between the two major ions, DNA and the second messenger c-di-AMP.

Cyclic-di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation inStaphylococcus aureusbut dispensable for viability in anaerobic conditions

“…It is tempting to speculate that the larger cell size observed in a strain with reduced cdi-AMP levels is at least in part due to an increase in potassium and osmolyte uptake, leading to an increase in osmotic pressure at low c-di-AMP levels. This is consistent with additional findings presented below and previous speculations made by us and others (23,26,35,37,39,40).…”

“…show changes in membrane potential and cell size. Experimental evidence suggests that c-di-AMP negatively regulates potassium uptake in bacteria (24,37,(39)(40)(41). Potassium is required for many cellular processes, including osmotic regulation and regulation of the membrane potential.…”

Metabolic basis of brain-like electrical signalling in bacterial communities

“…Notably, potassium and glutamate are the two most abundant ions in living cells [8]. In addition to their their roles in osmoregulation, pH maintenance and nitrogen metabolism, they are essential for information propagation in animal nervous systems.…”

Identification of the main glutamine and glutamate transporters inStaphylococcus aureusand their impact on c-di-AMP production

“…There is now considerable evidence that one such messenger, cyclic di-adenosine monophosphate (c-di-AMP) plays a significant role in osmoregulation in bacteria (Pham et al ., 2018, Pham & Turner, 2019, Quintana et al ., 2019, Zarrella et al ., 2018, Teh et al ., 2019, Fahmi et al ., 2019, Devaux et al ., 2018, Bai et al ., 2014, Zeden et al ., 2018, Corrigan et al ., 2011, Rocha et al ., 2019, Gundlach et al ., 2017b, Gundlach et al ., 2017a, Witte et al ., 2013, Whiteley et al ., 2015, Whiteley et al ., 2017). c-di-AMP binds to and negatively regulates a number of different potassium and osmolyte importers (Rocha et al ., 2019, Quintana et al ., 2019, Kim et al ., 2015, Corrigan et al ., 2013, Moscoso et al ., 2015, Chin et al ., 2015, Huynh et al ., 2016, Schuster et al ., 2016, Pham & Turner, 2019, Pham et al ., 2018, Devaux et al ., 2018, Zarrella et al ., 2018, Gundlach et al ., 2017b, Gundlach et al ., 2017a, Gundlach et al ., 2017c). c-di-AMP is essential for bacterial growth under standard growth conditions but it is also toxic at high levels in many Firmicutes, hence its cellular levels must be tightly regulated (Gundlach et al ., 2015b, Mehne et al ., 2013, Corrigan et al ., 2011, Corrigan et al ., 2015, Woodward et al ., 2010, Witte et al ., 2013).…”

“…Previously, we found that inactivation of the main glycine betaine transporter OpuD as well as the predicted amino acid transporter AlsT (SAUSA300_1252) allows an S. aureus dacA mutant to grow in rich medium in the absence of c-di-AMP (Zeden et al ., 2018). In several other Firmicutes, including B. subtilis, Lactococcus lactis, Streptococcus pneumoniae, Streptococcus pyogenes and L. monocytogenes , inactivating mutations have also been identified in osmolyte and potassium transport systems that allow these bacteria to grow in the absence of c-di-AMP (Pham et al ., 2018, Pham & Turner, 2019, Quintana et al ., 2019, Zarrella et al ., 2018, Teh et al ., 2019, Fahmi et al ., 2019, Devaux et al ., 2018, Bai et al ., 2014, Zeden et al ., 2018, Corrigan et al ., 2011, Rocha et al ., 2019, Gundlach et al ., 2017b, Gundlach et al ., 2017a, Witte et al ., 2013, Whiteley et al ., 2015, Whiteley et al ., 2017). This is consistent with the idea that in the absence of c-di-AMP, potassium and osmolyte transporters are more active, resulting in the accumulation of toxic levels of potassium and osmolytes in the cell.…”