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Screening of streptococcus pneumoniae ABC transporter mutants demonstrates that LivJHMGF, a branched-chain amino acid ABC transporter, is necessary for disease pathogenesis

  • Arthur Hosie
    ,
  • Shilpa Basavanna
    ,
  • S. Khandavilli
    ,
  • J. Yuste
    ,
  • J.M. Cohen
    ,
  • Alexander J. Webb
  • University College London
    ,
  • King's College London
    ,
  • University of York
Research Output: Contribution to journal Article Peer-review

Open access

Abstract

Bacterial ABC transporters are an important class of transmembrane transporters that have a wide variety of substrates and are important for the virulence of several bacterial pathogens, including Streptococcus pneumoniae. However, many S. pneumoniae ABC transporters have yet to be investigated for their role in virulence. Using insertional duplication mutagenesis mutants, we investigated the effects on virulence and in vitro growth of disruption of 9 S. pneumoniae ABC transporters. Several were partially attenuated in virulence compared to the wild-type parental strain in mouse models of infection. For one ABC transporter, required for full virulence and termed LivJHMGF due to its similarity to branched-chain amino acid (BCAA) transporters, a deletion mutant (ΔlivHMGF) was constructed to investigate its phenotype in more detail. When tested by competitive infection, the ΔlivHMGF strain had reduced virulence in models of both pneumonia and septicemia but was fully virulent when tested using noncompetitive experiments. The ΔlivHMGF strain had no detectable growth defect in defined or complete laboratory media. Recombinant LivJ, the substrate binding component of the LivJHMGF, was shown by both radioactive binding experiments and tryptophan fluorescence spectroscopy to specifically bind to leucine, isoleucine, and valine, confirming that the LivJHMGF substrates are BCAAs. These data demonstrate a previously unsuspected role for BCAA transport during infection for S. pneumoniae and provide more evidence that functioning ABC transporters are required for the full virulence of bacterial pathogens.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 3412-3423

Journal (Volume, Issue Number)

Infection and Immunity (Volume 77, Issue 8)

Publication milestones

  • Published - 01/08/2009

Publication status

Published - 01/08/2009

ISSN

0019-9567

External Publication IDs

  • handle.net: 10547/228314
  • Scopus: 67651233743

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