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.
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
Jeremy S
JS
Brown
Sarah M
SM
Gilliland
Javier
J
Ruiz-Albert
David W
DW
Holden
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