A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus

Maintaining manganese (Mn) homeostasis is important for the virulence of numerous bacteria. In the human respiratory pathogen Streptococcus pneumoniae, the Mn-specific importer PsaBCA, exporter MntE, and transcriptional regulator PsaR establish Mn homeostasis. In other bacteria, Mn homeostasis is co...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2019-07, Vol.47 (13), p.6885-6899
Main Authors: Martin, Julia E, Le, My T, Bhattarai, Nabin, Capdevila, Daiana A, Shen, Jiangchuan, Winkler, Malcolm E, Giedroc, David P
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - biosynthesis
Adenosine Triphosphatases - genetics
Aptamers, Nucleotide
Bacillus subtilis - genetics
Bacillus subtilis - metabolism
Bacterial Proteins - biosynthesis
Bacterial Proteins - genetics
Calcium - pharmacology
Gene Expression Regulation, Bacterial
Homeostasis
Manganese - metabolism
Manganese - pharmacology
Manganese - toxicity
Membrane Transport Proteins - biosynthesis
Membrane Transport Proteins - genetics
Molecular Biology
Nucleic Acid Conformation - drug effects
Riboswitch
RNA, Bacterial - genetics
RNA, Bacterial - metabolism
Streptococcus pneumoniae - genetics
Streptococcus pneumoniae - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Maintaining manganese (Mn) homeostasis is important for the virulence of numerous bacteria. In the human respiratory pathogen Streptococcus pneumoniae, the Mn-specific importer PsaBCA, exporter MntE, and transcriptional regulator PsaR establish Mn homeostasis. In other bacteria, Mn homeostasis is controlled by yybP-ykoY family riboswitches. Here, we characterize a yybP-ykoY family riboswitch upstream of the mgtA gene encoding a PII-type ATPase in S. pneumoniae, suggested previously to function in Ca2+ efflux. We show that the mgtA riboswitch aptamer domain adopts a canonical yybP-ykoY structure containing a three-way junction that is compacted in the presence of Ca2+ or Mn2+ at a physiological Mg2+ concentration. Although Ca2+ binds to the RNA aptamer with higher affinity than Mn2+, in vitro activation of transcription read-through of mgtA by Mn2+ is much greater than by Ca2+. Consistent with this result, mgtA mRNA and protein levels increase ≈5-fold during cellular Mn stress, but only in genetic backgrounds of S. pneumoniae and Bacillus subtilis that exhibit Mn2+ sensitivity, revealing that this riboswitch functions as a failsafe 'on' signal to prevent Mn2+ toxicity in the presence of high cellular Mn2+. In addition, our results suggest that the S. pneumoniae yybP-ykoY riboswitch functions to regulate Ca2+ efflux under these conditions.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkz494