The first histidine triad motif of phtd is critical for zinc homeostasis in Streptococcus pneumoniae

Eijkelkamp, B. A., Pederick, V. G., Plumptre, C. D., Harvey, R. M., Hughes, C. E. , Paton, J. C. and McDevitt, C. A. (2016) The first histidine triad motif of phtd is critical for zinc homeostasis in Streptococcus pneumoniae. Infection and Immunity, 84(2), pp. 407-415. (doi: 10.1128/IAI.01082-15) (PMID:26573735) (PMCID:PMC4730578)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hughes, Dr Catherine
Authors: Eijkelkamp, B. A., Pederick, V. G., Plumptre, C. D., Harvey, R. M., Hughes, C. E., Paton, J. C., and McDevitt, C. A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN:0019-9567
ISSN (Online):1098-5522
Published Online:16 November 2015
Copyright Holders:Copyright © 2016 American Society for Microbiology
First Published:First published in Infection and Immunity 84(2):407-415)

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