Overlapping functionality of the Pht proteins in zinc homeostasis of streptococcus pneumoniae

Plumptre, C. D., Hughes, C. E. , Harvey, R. M., Eijkelkamp, B. A., McDevitt, C. A. and Paton, J. C. (2014) Overlapping functionality of the Pht proteins in zinc homeostasis of streptococcus pneumoniae. Infection and Immunity, 82(10), pp. 4315-4324. (doi: 10.1128/IAI.02155-14) (PMID:25069983) (PMCID:PMC4187861)

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Streptococcus pneumoniae is a globally significant pathogen that causes a range of diseases, including pneumonia, sepsis, meningitis, and otitis media. Its ability to cause disease depends upon the acquisition of nutrients from its environment, including transition metal ions such as zinc. The pneumococcus employs a number of surface proteins to achieve this, among which are four highly similar polyhistidine triad (Pht) proteins. It has previously been established that these proteins collectively aid in the delivery of zinc to the ABC transporter substrate-binding protein AdcAII. Here we have investigated the contribution of each individual Pht protein to pneumococcal zinc homeostasis by analyzing mutant strains expressing only one of the four pht genes. Under conditions of low zinc availability, each of these mutants showed superior growth and zinc accumulation profiles relative to a mutant strain lacking all four genes, indicating that any of the four Pht proteins are able to facilitate delivery of zinc to AdcAII. However, optimal growth and zinc accumulation in vitro and pneumococcal survival and proliferation in vivo required production of all four Pht proteins, indicating that, despite their overlapping functionality, the proteins are not dispensable without incurring a fitness cost. We also show that surface-attached forms of the Pht proteins are required for zinc recruitment and that they do not contribute to defense against extracellular zinc stress.

Item Type:Articles
Additional Information:This work was supported by the National Health and Medical Research Council (NHMRC) (program grant 565526 to J.C.P. and project grant 1022240 to C.A.M.) and the Australian Research Council (discovery project grants DP120101432 and DP120103957 to J.C.P. and C.A.M., respectively).
Glasgow Author(s) Enlighten ID:Hughes, Dr Catherine
Authors: Plumptre, C. D., Hughes, C. E., Harvey, R. M., Eijkelkamp, B. A., McDevitt, C. A., and Paton, J. C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN (Online):1098-5522
Published Online:28 July 2014
Copyright Holders:Copyright © 2014 American Society for Microbiology
First Published:First published in Infection and Immunity 82(10):4315-4324
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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