Journal article
The zinc efflux activator SczA protects Streptococcus pneumoniae serotype 2 D39 from intracellular zinc toxicity
JE Martin, KA Edmonds, KE Bruce, GC Campanello, BA Eijkelkamp, EB Brazel, CA McDevitt, ME Winkler, DP Giedroc
Molecular Microbiology | WILEY | Published : 2017
DOI: 10.1111/mmi.13654
Abstract
Zinc is an essential trace element that serves as a catalytic cofactor in metalloenzymes and a structural element in proteins involved in general metabolism and cellular defenses of pathogenic bacteria. Despite its importance, high zinc levels can impair cellular processes, inhibiting growth of many pathogenic bacteria, including the major respiratory pathogen Streptococcus pneumoniae. Zinc intoxication is prevented in S. pneumoniae by expression of the zinc exporter CzcD, whose expression is activated by the novel TetR-family transcriptional zinc-sensing regulator SczA. How zinc bioavailability triggers activation of SczA is unknown. It is shown here through functional studies in S. pneumon..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Dr. John P. Lisher for help with ICP-MS analysis, Dr. Hongwei Wu for help in acquiring NMR spectra, and Adriana Giuliani and Katherine Geiger for help in early cloning of and in vitro mutagenesis experiments with S. pneumoniae SczA. This work was supported by NIH grants GM042569 and GM118157 (to D.P.G.), GM113172 and GM114315 (to M.E.W), and Australian Research Council Discovery Project Grant DP150101856 (to C.A.M). The NMR instrumentation in the METACyt Biomolecular NMR Laboratory at Indiana University was generously supported by a grant from the Lilly Endowment.