Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/99501
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: The first histidine triad motif of PhtD is critical for zinc homeostasis in Streptococcus pneumoniae
Author: Eijkelkamp, B.
Pederick, V.
Plumptre, C.
Harvey, R.
Hughes, C.
Paton, J.
McDevitt, C.
Citation: Infection and Immunity, 2015; 84(2):407-415
Publisher: American Society for Microbiology
Issue Date: 2015
ISSN: 0019-9567
1098-5522
Statement of
Responsibility: 
Bart A. Eijkelkamp, Victoria G. Pederick, Charles D. Plumptre, Richard M. Harvey, Catherine E. Hughes, James C. Paton, Christopher A. McDevitt
Abstract: Streptococcus pneumoniae is the world's foremost human pathogen. Acquisition of the first row transition metal ion zinc is essential for pneumococcal colonization and disease. Zinc is acquired via the ATP-binding cassette transporter AdcCB and two zinc-binding proteins, AdcA and AdcAII. We have previously shown that AdcAII is reliant upon the polyhistidine triad (Pht) proteins to aid in zinc recruitment. Pht proteins generally contain five histidine (His) triad motifs that are believed to facilitate zinc binding and therefore play a significant role in pneumococcal metal ion homeostasis. However, the importance and potential redundancy of these motifs have not been addressed. We examined the effects of mutating each of the five His triad motifs of PhtD. The combination of in vitro growth assays, active zinc uptake, and PhtD expression studies show that the His triad closest to the protein's amino terminus is the most important for zinc acquisition. Intriguingly, in vivo competitive infection studies investigating the amino- and carboxyl-terminal His triad mutants indicate that the motifs have similar importance in colonization. Collectively, our new insights into the contributions of the individual His triad motifs of PhtD, and by extension the other Pht proteins, highlight the crucial role of the first His triad site in zinc acquisition. This study also suggests that the Pht proteins likely play a role beyond zinc acquisition in pneumococcal virulence.
Keywords: Animals; Humans; Mice; Streptococcus pneumoniae; Zinc; Histidine; Bacterial Proteins; Amino Acid Motifs; Homeostasis; Mutation; Genetic Fitness; Bacterial Load
Rights: Copyright © 2016, American Society for Microbiology. All Rights Reserved.
RMID: 0030039701
DOI: 10.1128/IAI.01082-15
Grant ID: http://purl.org/au-research/grants/arc/DP120101432
http://purl.org/au-research/grants/arc/DP120103957
http://purl.org/au-research/grants/arc/DP150101856
http://purl.org/au-research/grants/nhmrc/565526
http://purl.org/au-research/grants/nhmrc/1071659
http://purl.org/au-research/grants/nhmrc/1022240
http://purl.org/au-research/grants/nhmrc/1080784
Appears in Collections:Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.