2.50
Hdl Handle:
http://hdl.handle.net/10033/214850
Title:
Impact of glutamine transporters on pneumococcal fitness under infection-related conditions.
Authors:
Härtel, Tobias; Klein, Matthias; Koedel, Uwe; Rohde, Manfred; Petruschka, Lothar; Hammerschmidt, Sven
Abstract:
The genomic analysis of Streptococcus pneumoniae predicted six putative glutamine uptake systems, which are expressed under in vitro conditions, as shown here by reverse transcription-PCR. Four of these operons consist of glnHPQ, while two lack glnH, which encodes a soluble glutamine-binding protein. Here, we studied the impact of two of these glutamine ATP-binding cassette transporters on S. pneumoniae D39 virulence and phagocytosis, which consist of GlnQ and a translationally fused protein of GlnH and GlnP. Mice infected intranasally with D39Δgln0411/0412 showed significantly increased survival times and a significant delay in the development of pneumococcal pneumonia compared to those infected with D39, as observed in real time using bioluminescent pneumococci. In a mouse sepsis model, the mutant D39Δgln0411/0412 showed only moderate but significant attenuation. In contrast, the D39Δgln1098/1099 knockout strain was massively attenuated in the pneumonia and septicemia mouse infection model. To cause pneumonia or sepsis with D39Δgln1098/1099, infection doses 100- to 10,000-fold higher than those used for wild-type strain D39 were required. In an experimental mouse meningitis model, D39Δgln1098/1099 produced decreased levels of white blood cells in cerebrospinal fluid and showed decreased numbers of bacteria in the bloodstream compared to D39 and D39Δgln0411/0412. Phagocytosis experiments revealed significantly decreased intracellular survival rates of mutants D39Δgln1098/1099 and D39Δgln0411/0412 compared to wild-type D39, suggesting that the deficiency of Gln uptake systems impairs resistance to oxidative stress. Taken together, our results demonstrate that both glutamine uptake systems are required for full virulence of pneumococci but exhibit different impacts on the pathogenesis of pneumococci under in vivo conditions.
Affiliation:
Department of Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt Universität Greifswald, Friedrich-Ludwig-Jahn-Str. 15a, D-17487 Greifswald, Germany.
Citation:
Impact of glutamine transporters on pneumococcal fitness under infection-related conditions. 2011, 79 (1):44-58 Infect. Immun.
Journal:
Infection and immunity
Issue Date:
Jan-2011
URI:
http://hdl.handle.net/10033/214850
DOI:
10.1128/IAI.00855-10
PubMed ID:
21078855
Type:
Article
Language:
en
ISSN:
1098-5522
Appears in Collections:
Publications of Dept. Medizinische Mikrobiologie (MMIK)

Full metadata record

DC FieldValue Language
dc.contributor.authorHärtel, Tobiasen_GB
dc.contributor.authorKlein, Matthiasen_GB
dc.contributor.authorKoedel, Uween_GB
dc.contributor.authorRohde, Manfreden_GB
dc.contributor.authorPetruschka, Lotharen_GB
dc.contributor.authorHammerschmidt, Svenen_GB
dc.date.accessioned2012-03-08T14:59:12Z-
dc.date.available2012-03-08T14:59:12Z-
dc.date.issued2011-01-
dc.identifier.citationImpact of glutamine transporters on pneumococcal fitness under infection-related conditions. 2011, 79 (1):44-58 Infect. Immun.en_GB
dc.identifier.issn1098-5522-
dc.identifier.pmid21078855-
dc.identifier.doi10.1128/IAI.00855-10-
dc.identifier.urihttp://hdl.handle.net/10033/214850-
dc.description.abstractThe genomic analysis of Streptococcus pneumoniae predicted six putative glutamine uptake systems, which are expressed under in vitro conditions, as shown here by reverse transcription-PCR. Four of these operons consist of glnHPQ, while two lack glnH, which encodes a soluble glutamine-binding protein. Here, we studied the impact of two of these glutamine ATP-binding cassette transporters on S. pneumoniae D39 virulence and phagocytosis, which consist of GlnQ and a translationally fused protein of GlnH and GlnP. Mice infected intranasally with D39Δgln0411/0412 showed significantly increased survival times and a significant delay in the development of pneumococcal pneumonia compared to those infected with D39, as observed in real time using bioluminescent pneumococci. In a mouse sepsis model, the mutant D39Δgln0411/0412 showed only moderate but significant attenuation. In contrast, the D39Δgln1098/1099 knockout strain was massively attenuated in the pneumonia and septicemia mouse infection model. To cause pneumonia or sepsis with D39Δgln1098/1099, infection doses 100- to 10,000-fold higher than those used for wild-type strain D39 were required. In an experimental mouse meningitis model, D39Δgln1098/1099 produced decreased levels of white blood cells in cerebrospinal fluid and showed decreased numbers of bacteria in the bloodstream compared to D39 and D39Δgln0411/0412. Phagocytosis experiments revealed significantly decreased intracellular survival rates of mutants D39Δgln1098/1099 and D39Δgln0411/0412 compared to wild-type D39, suggesting that the deficiency of Gln uptake systems impairs resistance to oxidative stress. Taken together, our results demonstrate that both glutamine uptake systems are required for full virulence of pneumococci but exhibit different impacts on the pathogenesis of pneumococci under in vivo conditions.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Infection and immunityen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshBacterial Proteinsen_GB
dc.subject.meshCarrier Proteinsen_GB
dc.subject.meshCell Lineen_GB
dc.subject.meshComputational Biologyen_GB
dc.subject.meshGene Expression Regulation, Bacterialen_GB
dc.subject.meshMeningitis, Bacterialen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMutationen_GB
dc.subject.meshPneumococcal Infectionsen_GB
dc.subject.meshStreptococcus pneumoniaeen_GB
dc.titleImpact of glutamine transporters on pneumococcal fitness under infection-related conditions.en
dc.typeArticleen
dc.contributor.departmentDepartment of Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt Universität Greifswald, Friedrich-Ludwig-Jahn-Str. 15a, D-17487 Greifswald, Germany.en_GB
dc.identifier.journalInfection and immunityen_GB

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