Document Detail


A Francisella tularensis locus required for spermine responsiveness is necessary for virulence.
MedLine Citation:
PMID:  21670171     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-13
Journal Detail:
Title:  Infection and immunity     Volume:  79     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-17     Completed Date:  2011-10-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3665-76     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, 200 Lothrop St., Pittsburgh, PA 15261, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
AI074402/AI/NIAID NIH HHS; P30 DK040561-15/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Chemokines; 0/Cytokines; 71-44-3/Spermine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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