Abstract
Across bacterial species, metal binding proteins can serve functions in pathogenesis in addition to regulating metal homeostasis. We have compared and contrasted the activities of zinc (Zn2+)-binding lipoproteins AdcA and AdcAII in the Streptococcus pneumoniae TIGR4 background. Exposure to Zn2+-limiting conditions resulted in delayed growth in a strain lacking AdcAII (ΔAdcAII) when compared to wild type bacteria or a mutant lacking AdcA (ΔAdcA). AdcAII failed to interact with the extracellular matrix protein laminin despite homology to laminin-binding proteins of related streptococci. Deletion of AdcA or AdcAII led to significantly increased invasion of A549 human lung epithelial cells and a trend toward increased invasion in vivo. Loss of AdcAII, but not AdcA, was shown to negatively impact early colonization of the nasopharynx. Our findings suggest that expression of AdcAII affects invasiveness of S. pneumoniae in response to available Zn2+ concentrations.
Highlights
Streptococcus pneumoniae normally colonizes the human nasopharynx asymptomatically, but can cause serious infections, including pneumonia, septicemia, and bacterial meningitis
Adhesion of pneumococci to nasopharyngeal epithelial cells is reduced by antibodies to PsaA, [3] and PsaA has been proven essential for virulence in animal models when inoculated intranasally [4]
Previous work in the laboratory-adapted strains D39 and R6 have shown that expression of both adcA and adcAII is important for growth in low Zn2+ conditions [12, 27]
Summary
Streptococcus pneumoniae normally colonizes the human nasopharynx asymptomatically, but can cause serious infections, including pneumonia, septicemia, and bacterial meningitis. The pneumococcus is able to adapt to a wide variety of host environments. A key question is whether these metal transporters have additional functions such as directly affecting adherence to host cells or the extracellular matrix. The LraI (lipoprotein receptor antigen I) family of lipoproteins represents one group of metal transporters. Characterized proteins within the LraI family, including the manganese-binding protein PsaA from S. pneumoniae, play roles in both adhesion and metal transport [1, 2]. Adhesion of pneumococci to nasopharyngeal epithelial cells is reduced by antibodies to PsaA, [3] and PsaA has been proven essential for virulence in animal models when inoculated intranasally [4]
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