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AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in S treptococcus pneumoniae
Author(s) -
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.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12504
Subject(s) - zinc , biology , plasma protein binding , zinc finger , biochemistry , binding site , microbiology and biotechnology , genetics , gene , chemistry , transcription factor , organic chemistry
Summary S treptococcus 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 G ram‐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.