title: A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence.
abstract: Restricted iron availability is a major obstacle to growth and survival of pathogenic bacteria during infection. In contrast to Gram-negative pathogens, little is known about how Gram-positive pathogens obtain this essential metal. We have identified two Streptococcus pneumoniae genetic loci, pit1 and pit2, encoding homologues of ABC iron transporters that are required for iron uptake by this organism. S. pneumoniae strains containing disrupted copies of either pit1 or pit2 had decreased sensitivity to the iron-dependent antibiotic streptonigrin, and a strain containing disrupted copies of both pit1 and pit2 was unable to use haemoglobin as an iron source and had a reduced rate of iron uptake. The pit2- strain was moderately and the pit1-/pit2- strain strongly attenuated in virulence in mouse models of pulmonary and systemic infection, showing that the pit loci play a critical role during in vivo growth of S. pneumoniae. The pit2 locus is contained within a 27 kb region of chromosomal DNA that has several features of Gram-negative bacterial pathogenicity islands. This probable pathogenicity island (PPI-1) is the first to be described for S. pneumoniae, and its acquisition is likely to have played a significant role in the evolution of this important human pathogen.
authors.affiliation: Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Brown
authors.forename: S M
authors.initials: SM
authors.lastname: Gilliland
authors.forename: D W
authors.initials: DW
authors.lastname: Holden
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002712:Chlorides; D004195:Disease Models, Animal; D005290:Ferric Compounds / Q000493:pharmacokinetics; D005798:Genes, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D011008:Pneumococcal Infections / Q000382:microbiology; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D013308:Streptonigrin / Q000494:pharmacology; D014774:Virulence
chemical_list: D018528:ATP-Binding Cassette Transporters; D002712:Chlorides; D005290:Ferric Compounds; D013308:Streptonigrin; D007501:Iron; C024555:ferric chloride