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

2.50
Hdl Handle:
http://hdl.handle.net/10547/228314
Title:
Screening of streptococcus pneumoniae ABC transporter mutants demonstrates that LivJHMGF, a branched-chain amino acid ABC transporter, is necessary for disease pathogenesis
Authors:
Basavanna, Shilpa; Khandavilli, S.; Yuste, J.; Cohen, J.M.; Hosie, Arthur H.F. ( 0000-0002-1327-7901 ) ; Webb, Alexander J.; Thomas, Gavin H.; Brown, Jeremy S.
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.
Affiliation:
Royal Free and University College Medical School; University College London; King's College London Dental Institute; University of York
Citation:
Basavanna, S. et al (2009) 'Screening of streptococcus pneumoniae ABC transporter mutants demonstrates that LivJHMGF, a branched-chain amino acid ABC transporter, is necessary for disease pathogenesis' Infection and Immunity 77 (8):3412-3423
Publisher:
American Society for Microbiology
Journal:
Infection and Immunity
Issue Date:
Aug-2009
URI:
http://hdl.handle.net/10547/228314
DOI:
10.1128/IAI.01543-08
Additional Links:
http://iai.asm.org/cgi/doi/10.1128/IAI.01543-08
Type:
Article
Language:
en
ISSN:
0019-9567
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorBasavanna, Shilpaen_GB
dc.contributor.authorKhandavilli, S.en_GB
dc.contributor.authorYuste, J.en_GB
dc.contributor.authorCohen, J.M.en_GB
dc.contributor.authorHosie, Arthur H.F.en_GB
dc.contributor.authorWebb, Alexander J.en_GB
dc.contributor.authorThomas, Gavin H.en_GB
dc.contributor.authorBrown, Jeremy S.en_GB
dc.date.accessioned2012-06-11T10:11:15Zen
dc.date.available2012-06-11T10:11:15Zen
dc.date.issued2009-08en
dc.identifier.citationBasavanna, S. et al (2009) 'Screening of streptococcus pneumoniae ABC transporter mutants demonstrates that LivJHMGF, a branched-chain amino acid ABC transporter, is necessary for disease pathogenesis' Infection and Immunity 77 (8):3412-3423en_GB
dc.identifier.issn0019-9567en
dc.identifier.doi10.1128/IAI.01543-08en
dc.identifier.urihttp://hdl.handle.net/10547/228314en
dc.description.abstractBacterial 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.en_GB
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen_GB
dc.relation.urlhttp://iai.asm.org/cgi/doi/10.1128/IAI.01543-08en_GB
dc.rightsArchived with thanks to Infection and Immunityen_GB
dc.subjecttransmembrane transportersen
dc.subjectStreptococcus pneumoniaeen
dc.subjectbacterial pathogensen
dc.titleScreening of streptococcus pneumoniae ABC transporter mutants demonstrates that LivJHMGF, a branched-chain amino acid ABC transporter, is necessary for disease pathogenesisen
dc.typeArticleen
dc.contributor.departmentRoyal Free and University College Medical Schoolen_GB
dc.contributor.departmentUniversity College Londonen
dc.contributor.departmentKing's College London Dental Instituteen
dc.contributor.departmentUniversity of Yorken
dc.identifier.journalInfection and Immunityen_GB
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