AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae

Plumptre, Charles D., Eijkelkamp, Bart A., Morey, Jacqueline R., Behr, Felix, Couñago, Rafael M., Ogunniyi, Abiodun D., Kobe, Bostjan, O'Mara, Megan L., Paton, James C. and McDevitt, Christopher A. (2014) AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae. Molecular Microbiology, 91 4: 834–851-834–851. doi:10.1111/mmi.12504


Author Plumptre, Charles D.
Eijkelkamp, Bart A.
Morey, Jacqueline R.
Behr, Felix
Couñago, Rafael M.
Ogunniyi, Abiodun D.
Kobe, Bostjan
O'Mara, Megan L.
Paton, James C.
McDevitt, Christopher A.
Title AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae
Formatted title
AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae
Journal name Molecular Microbiology   Check publisher's open access policy
ISSN 0950-382X
1365-2958
Publication date 2014-02-01
Year available 2014
Sub-type Article (original research)
DOI 10.1111/mmi.12504
Open Access Status Not yet assessed
Volume 91
Issue 4
Start page 834–851
End page 834–851
Total pages 18
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Streptococcus pneumoniae is a globally significant human pathogen responsible for nearly 1 million deaths annually. Central to the ability of S.pneumoniae to colonize and mediate disease in humans is the acquisition of zinc from the host environment. Zinc uptake in S.pneumoniae occurs via the ATP-binding cassette transporter AdcCB, and, unusually, two zinc-binding proteins, AdcA and AdcAII. Studies have suggested that these two proteins are functionally redundant, although AdcA has remained uncharacterized by biochemical methods. Here we show that AdcA is a zinc-specific substrate-binding protein (SBP). By contrast with other zinc-binding SBPs, AdcA has two zinc-binding domains: a canonical amino-terminal cluster A-I zinc-binding domain and a carboxy-terminal zinc-binding domain, which has homology to the zinc-chaperone ZinT from Gram-negative organisms. Intriguingly, this latter feature is absent from AdcAII and suggests that the two zinc-binding SBPs of S.pneumoniae employ different modalities in zinc recruitment. We further show that AdcAII is reliant upon the polyhistidine triad proteins for zinc in vitro and in vivo. Collectively, our studies suggest that, despite the overlapping roles of the two SBPs in zinc acquisition, they may have unique mechanisms in zinc homeostasis and act in a complementary manner during host colonization.
Formatted abstract
Streptococcus pneumoniae is a globally significant human pathogen responsible for nearly 1 million deaths annually. Central to the ability of S. pneumoniae to colonize and mediate disease in humans is the acquisition of zinc from the host environment. Zinc uptake in S. pneumoniae occurs via the ATP-binding cassette transporter AdcCB, and, unusually, two zinc-binding proteins, AdcA and AdcAII. Studies have suggested that these two proteins are functionally redundant, although AdcA has remained uncharacterized by biochemical methods. Here we show that AdcA is a zinc-specific substrate-binding protein (SBP). By contrast with other zinc-binding SBPs, AdcA has two zinc-binding domains: a canonical amino-terminal cluster A-I zinc-binding domain and a carboxy-terminal zinc-binding domain, which has homology to the zinc-chaperone ZinT from Gram-negative organisms. Intriguingly, this latter feature is absent from AdcAII and suggests that the two zinc-binding SBPs of S. pneumoniae employ different modalities in zinc recruitment. We further show that AdcAII is reliant upon the polyhistidine triad proteins for zinc in vitro and in vivo. Collectively, our studies suggest that, despite the overlapping roles of the two SBPs in zinc acquisition, they may have unique mechanisms in zinc homeostasis and act in a complementary manner during host colonization.
Keyword Biochemistry & Molecular Biology
Microbiology
Biochemistry & Molecular Biology
Microbiology
BIOCHEMISTRY & MOLECULAR BIOLOGY
MICROBIOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP120103957
1022240
Institutional Status UQ

 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 25 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 14 Feb 2014, 19:22:41 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences