A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence

Restricted iron availability is a major obstacle to growth and survival of pathogenic bacteria during infection. In contrast to Gram-negative pathogen s, little is known about how Gram-positive pathogens obtain this essential metal. We have identified two Streptococcus pneumoniae genetic loci, pit1 a nd pit2, encoding homologues of ABC iron transporters that are required for iron uptake by this organism. S. pneumoniae strains containing disrupted c opies of either pit1 or pit2 had decreased sensitivity to the iron-dependen t antibiotic streptonigrin, and a strain containing disrupted copies of bot h pit1 and pit2 was unable to use haemoglobin as an iron source and had a r educed rate of iron uptake. The pit2(-) strain was moderately and the pit1( -)/pit2(-) strain strongly attenuated in virulence in mouse models of pulmo nary 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-negati ve 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.