Characterization of pit, a Streptococcus pneumoniae iron uptake ABC transporter.
Bacteria frequently have multiple mechanisms for acquiring iron, an essential micronutrient, from the environment. We have identified a four-gene Streptococcus pneumoniae operon, named pit, encoding proteins with similarity to components of a putative Brachyspira hyodysenteriae iron uptake ABC transporter, Bit. An S. pneumoniae strain containing a defined mutation in pit has impaired growth in medium containing the iron chelator ethylenediamine di-o-hydroxyphenylacetic acid, reduced sensitivity to the iron-dependent antibiotic streptonigrin, and impaired virulence in a mouse model of S. pneumoniae systemic infection. Furthermore, addition of a mutation in pit to a strain containing mutations in the two previously described S. pneumoniae iron uptake ABC transporters, piu and pia, resulted in a strain with impaired growth in two types of iron-deficient medium, a high degree of resistance to streptonigrin, and a reduced rate of iron uptake. Comparison of the susceptibilities to streptonigrin of the individual pit, piu, and pia mutant strains and comparison of the growth in iron-deficient medium and virulence of single and double mutant strains suggest that pia is the dominant iron transporter during in vitro and in vivo growth.
Brown
Jeremy S
JS
Centre for Molecular Microbiology and Infection, Department of Infectious Diseases, Faculty of Medicine, Imperial College School of Medicine, London SW7 2AZ, United Kingdom. jerry.brown@ic.ac.uk
Gilliland
Sarah M
SM
Ruiz-Albert
Javier
J
Holden
David W
DW
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics*; D002712:Chlorides; D003470:Culture Media; D005290:Ferric Compounds / Q000493:pharmacokinetics; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D016296:Mutagenesis; D009876:Operon; D033902:Periplasmic Binding Proteins; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D013308:Streptonigrin / Q000494:pharmacology; D014158:Transcription, Genetic; D014774:Virulence
D018528:ATP-Binding Cassette Transporters; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002712:Chlorides; D003470:Culture Media; D005290:Ferric Compounds; D033862:Iron-Binding Proteins; D033902:Periplasmic Binding Proteins; D013308:Streptonigrin; D007501:Iron; C024555:ferric chloride