title: AdcAII of Streptococcus pneumoniae Affects Pneumococcal Invasiveness.
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.
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS, 39762, United States of America.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Brown
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS, 39762, United States of America.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Gunnell
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS, 39762, United States of America.
authors.forename: Adam N
authors.initials: AN
authors.lastname: Cassella
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson, MS, 39216, United States of America.
authors.forename: Lance E
authors.initials: LE
authors.lastname: Keller
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, United States of America.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Scherkenbach
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, United States of America.
authors.forename: Beth
authors.initials: B
authors.lastname: Mann
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS, 39762, United States of America.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Brown
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS, 39762, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hill
authors.affiliation: Department of Chemistry, Mississippi State University, Mississippi State, MS, 39762, United States of America.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Fitzkee
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, United States of America.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Rosch
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, 38105, United States of America.
authors.forename: Elaine I
authors.initials: EI
authors.lastname: Tuomanen
authors.affiliation: Department of Biological Sciences, Mississippi State University, Mississippi State, MS, 39762, United States of America.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Thornton
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D009154:Mutation; D009305:Nasopharynx / Q000382:microbiology*; D020411:Oligonucleotide Array Sequence Analysis; D011008:Pneumococcal Infections / Q000382:microbiology*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000378:metabolism* / Q000472:pathogenicity*; D015032:Zinc / Q000737:chemistry*
chemical_list: D018528:ATP-Binding Cassette Transporters; C114936:AdcA protein, Streptococcus; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D007797:Laminin; D015032:Zinc