ATP reduction by MgtC and Mg²⁺ homeostasis by MgtA and MgtB enables Salmonella to accumulate RpoS upon low cytoplasmic Mg²⁺ stress

Abstract

RpoS is one of several alternative sigma factors known to alter gene expression profiles by RpoS-associated RNA polymerase in response to a variety of stresses. The enteric bacteria Salmonella enterica and Escherichia coli accumulate RpoS under low Mg concentrations via a common mechanism in which the PhoP regulator activates expression of antiadaptor proteins that, by sequestering the adaptor RssB, prevent RpoS degradation by the protease ClpXP. Here, we demonstrate that this genetic program alone does not fully support RpoS accumulation when cytoplasmic Mg concentration drops to levels that impair protein synthesis. Under these circumstances, only S. enterica continues RpoS accumulation in a manner dependent on other PhoP-activated programs (i.e. ATP reduction by the MgtC protein and Mg import by the MgtA and MgtB transporters) that maintain translation homeostasis. Moreover, we provide evidence that the mgtC gene, which is present in S. enterica but not in E. coli, is responsible for the differences in RpoS accumulation between these two bacterial species. Our results suggest that bacteria possess a mechanism to control RpoS accumulation responding to cytoplasmic Mg levels, the difference of which causes distinct RpoS accumulation in closely related bacterial species.

The role of rpoS in the regulation of Vibrio alginolyticus virulence and the response to diverse stresses

“…As a result, in order to better understand the virulence mechanism of pathogens, many studies were devoted to elucidating key genes related to stress resistance (Gupta et al, 2019;Tian et al, 2008). Among these, RpoS was proved to enable transcription of genes associated with the general stress response and stationary phase metabolism (Campos-Gomez & Benitez, 2018;Park, Nam, Kweon, & Shin, 2018). Meanwhile, rpoS was closely related to the virulence regulation of pathogenic bacteria (Xiao et al, 2009;Yin et al, 2018).…”

Residue L193P Mutant of RpoS Affects Its Activity During Biofilm Formation in Salmonella Pullorum

“…RpoS combines with RNA polymerase (RNAP) to regulate many genes by binding to gene promotors and initiating transcription that enables bacteria to survive adverse conditions (37,38). Research also showed that missense mutants in RpoS can affect its function including interacting with RNAP in E. coli (STEC) isolates.…”

Limitation of phosphate assimilation maintains cytoplasmic magnesium homeostasis

“…Notably, a Salmonella mgtC atpB double mutant strain-containing a genetically inactive ATP synthase-was also reported to harbor lower ATP levels than an mgtC single mutant strain during cytoplasmic Mg 2+ starvation (30). This result led to the notion that MgtC also prevents a non-physiological rise in ATP levels by inhibiting the F 1 F O ATP synthase when Salmonella experiences cytoplasmic Mg 2+ starvation (30,39,40). However, because the biochemical function of MgtC during cytoplasmic Mg 2+ starvation can be genetically separated from its function during intramacrophage replication (32), we sought to reexamine the interpretation of the aforementioned experimental results.…”