| A Francisella tularensis locus required for spermine responsiveness is necessary for virulence. | |
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MedLine Citation:
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PMID: 21670171 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tularemia is a debilitating febrile illness caused by the category A biodefense agent Francisella tularensis. This pathogen infects over 250 different hosts, has a low infectious dose, and causes high morbidity and mortality. Our understanding of the mechanisms by which F. tularensis senses and adapts to host environments is incomplete. Polyamines, including spermine, regulate the interactions of F. tularensis with host cells. However, it is not known whether responsiveness to polyamines is necessary for the virulence of the organism. Through transposon mutagenesis of F. tularensis subsp. holarctica live vaccine strain (LVS), we identified FTL_0883 as a gene important for spermine responsiveness. In-frame deletion mutants of FTL_0883 and FTT_0615c, the homologue of FTL_0883 in F. tularensis subsp. tularensis Schu S4 (Schu S4), elicited higher levels of cytokines from human and murine macrophages compared to wild-type strains. Although deletion of FTL_0883 attenuated LVS replication within macrophages in vitro, the Schu S4 mutant with a deletion in FTT_0615c replicated similarly to wild-type Schu S4. Nevertheless, both the LVS and the Schu S4 mutants were significantly attenuated in vivo. Growth and dissemination of the Schu S4 mutant was severely reduced in the murine model of pneumonic tularemia. This attenuation depended on host responses to elevated levels of proinflammatory cytokines. These data associate responsiveness to polyamines with tularemia pathogenesis and define FTL_0883/FTT_0615c as an F. tularensis gene important for virulence and evasion of the host immune response. |
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Authors:
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Brian C Russo; Joseph Horzempa; Dawn M O'Dee; Deanna M Schmitt; Matthew J Brown; Paul E Carlson; Ramnik J Xavier; Gerard J Nau |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-06-13 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-17 Completed Date: 2011-10-21 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 3665-76 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15261, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacterial Proteins / genetics*, physiology Cells, Cultured Chemokines / biosynthesis, immunology Cytokines / biosynthesis, immunology Enzyme-Linked Immunosorbent Assay Female Francisella tularensis / genetics*, growth & development, immunology, pathogenicity* Host-Pathogen Interactions Humans Macrophages / microbiology Mice Mice, Inbred C57BL Mutagenesis Polymerase Chain Reaction Sequence Deletion Spermine / metabolism* Tularemia / immunology, microbiology* |
| Grant Support | |
ID/Acronym/Agency:
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AI074402/AI/NIAID NIH HHS; P30 DK040561-15/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bacterial Proteins; 0/Chemokines; 0/Cytokines; 71-44-3/Spermine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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