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https://hdl.handle.net/2440/99501
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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, 2016; 84(2):407-415 |
Publisher: | American Society for Microbiology |
Issue Date: | 2016 |
ISSN: | 0019-9567 1098-5522 |
Editor: | Camilli, A. |
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. |
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 |
Published version: | http://dx.doi.org/10.1128/iai.01082-15 |
Appears in Collections: | Aurora harvest 3 Molecular and Biomedical Science publications |
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