An Intimate Link: Two-Component Signal Transduction Systems and Metal Transport Systems in Bacteria

Abstract

Bacteria have evolved various strategies to contend with high concentrations of environmental heavy metal ions for rapid, adaptive responses to maintain cell viability. Evidence gathered in the past two decades suggests that bacterial two-component signal transduction systems (TCSTSs) are intimately involved in monitoring cation accumulation, and can regulate the expression of related metabolic and virulence genes to elicit adaptive responses to changes in the concentration of these ions. Using examples garnered from recent studies, we summarize the cross-regulatory relationships between metal ions and TCSTSs. We present evidence of how bacterial TCSTSs modulate metal ion homeostasis and also how metal ions, in turn, function to control the activities of these signaling systems linked with bacterial survival and virulence. KEYWORDS• gene regulation • transition metal ion homoeostasis • two-component signal transduction systemsBacterial interactions with transition metal ions present a dual challenge: while many metal ions are biologically necessary at low levels, they can also be toxic at high concentrations. Bacteria use metal ions as cofactors for the function of several critical enzymes involved in electron transport and/or cell metabolism [1][2][3][4]. Accumulation of metal ions can impose deleterious effects on metabolic and cellular pathways thus compromising cell survival: different metal ions in the cytoplasm can tend to displace the metal cofactors at the active site(s) of enzymes ultimately leading to their inactivation [2,5]. For instance, when cellular metal homeostasis is disrupted, metals at the upper end of the Irving-Williams series -Mn(II) < Fe(II) < Co(II) < Ni(II) < Cu(II) > Zn(II) -have the potential to displace enzymatic metal cofactors at the lower end, thus rendering the proteins inactive [5,6]. In other cases, metal ions can also affect cell growth and viability by disrupting the structure of nucleic acids, phospholipid membranes and enzyme function [7,8]. Therefore, bacteria have developed complex mechanisms to monitor cellular metal ion levels and simultaneously maintain the homeostasis of multiple cations within a cell [9,10].Bacteria use various strategies to regulate heavy metal homeostasis, which include the use of metal efflux pumps, channels, cation-specific metalloregulatory proteins, small noncoding RNAs and two-component signal transduction systems (TCSTSs) [2]. The intracellular import of metal ions is often facilitated by ATP-binding cassette transporters and Nramp transporters, whereas their export is usually carried out by cation diffusion facilitators [11], P-type ATPases [12,13] and tripartite resistance-nodulation-cell division (RND) transporters [14]. The regulation of metal trafficking proteins or their encoding genes is usually modulated by TCSTSs or metalloregulatory proteins. Bacterial TCSTSs are comprised of a membrane-bound histidine kinase (HK) and an intracellular cognate response regulator (RR) protein [15]. Upon reaching an appropriate threshold signa...

Gene transcription patterns and energy reserves in Daphnia magna show no nanoparticle specific toxicity when exposed to ZnO and CuO nanoparticles.

“…When extracellular molecules bind to these receptors a biochemical chain of reactions, better known as signal transduction, can occur (Horton et al, 2006). It has been shown that metal ions can trigger signal transduction systems which can regulate the expression of genes to evoke responses to changes in the metal ion concentration in bacteria (Singh et al, 2014). Also in our study, effects of zinc on signal transduction were observed.…”

A two-component system gene SACE_0101 regulates copper homeostasis in Saccharopolyspora erythraea

“…To maintain the copper homeostasis, cytosolic copper is precisely regulated by resistance proteins. The twocomponent system was previously confirmed as the key regulatory system for the extra-cytoplasmic sensing of elevated copper ion and can regulate the expression of related genes to elicit adaptive responses to changes in the concentration of copper (Chaplin et al 2015;Singh et al 2014). Here, we found a total of 8 genes in the genome of S. erythraea NRRL23338 that are potentially involved in copper metabolism.…”

Multiple signaling systems target a core set of transition metal homeostasis genes using similar binding motifs

“…Some of the targets (Psest_0600 and Psest_1596) belong to P‐type ATPase family of transporters, which contains copper tolerance genes from Escherichia coli and other bacteria (Cha and Cooksey, ; Rowland and Niederweis, ). Interestingly, co‐evolution of TCSs and transporters has been explored in Firmicutes TCS and ABC transport systems (Dintner et al ., ; Gebhard, ), and has also been observed in other bacteria (Singh et al ., ). The second prominent category of copper resistance genes involved in copper tolerance includes multicopper oxidases.…”

“…At the same time, several known copper resistance genes (e.g., copA1 , copB1 , copA2 , copB2 ) did not demonstrate a copper‐specific phenotype in that study. Transition metals are known to have interrelated and complex impact on microbial physiology often triggering overlapping response (Singh et al ., ). Coordinated interactions may be required for the optimal final response and has been reported for the copper‐ and zinc‐responsive regulators in P. aeruginosa (Caille et al ., ) and copper‐responsive regulators in Salmonella sp (Pezza et al ., ).…”