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Characterization of tetratricopeptide repeat-like proteins in Francisella tularensis and identification of a novel locus required for virulence
V. Dankova, L. Balonova, A. Straskova, P. Spidlova, D. Putzova, T. Kijek, J. Bozue, C. Cote, S. Mou, P. Worsham, B. Szotakova, L. Cerveny, J. Stulik,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1970 to 6 months ago
Freely Accessible Science Journals
from 1995 to 6 months ago
PubMed Central
from 1970 to 1 year ago
Europe PubMed Central
from 1970 to 6 months ago
Open Access Digital Library
from 1970-01-01
Open Access Digital Library
from 1970-01-01
PubMed
25245806
DOI
10.1128/iai.01620-14
Knihovny.cz E-resources
- MeSH
- Bacterial Proteins genetics metabolism MeSH
- Cytosol microbiology MeSH
- Virulence Factors genetics metabolism MeSH
- Francisella tularensis genetics growth & development physiology MeSH
- Genetic Loci * MeSH
- Gene Knockout Techniques MeSH
- Mutagenesis, Insertional MeSH
- Macrophages microbiology MeSH
- Disease Models, Animal MeSH
- Mice, Inbred BALB C MeSH
- Tularemia microbiology pathology MeSH
- Virulence MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Francisella tularensis is a highly infectious bacterium that causes the potentially lethal disease tularemia. This extremely virulent bacterium is able to replicate in the cytosolic compartments of infected macrophages. To invade macrophages and to cope with their intracellular environment, Francisella requires multiple virulence factors, which are still being identified. Proteins containing tetratricopeptide repeat (TPR)-like domains seem to be promising targets to investigate, since these proteins have been reported to be directly involved in virulence-associated functions of bacterial pathogens. Here, we studied the role of the FTS_0201, FTS_0778, and FTS_1680 genes, which encode putative TPR-like proteins in Francisella tularensis subsp. holarctica FSC200. Mutants defective in protein expression were prepared by TargeTron insertion mutagenesis. We found that the locus FTS_1680 and its ortholog FTT_0166c in the highly virulent Francisella tularensis type A strain SchuS4 are required for proper intracellular replication, full virulence in mice, and heat stress tolerance. Additionally, the FTS_1680-encoded protein was identified as a membrane-associated protein required for full cytopathogenicity in macrophages. Our study thus identifies FTS_1680/FTT_0166c as a new virulence factor in Francisella tularensis.
References provided by Crossref.org
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- $a Dankova, Vera $u Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic Institute of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
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- $a Francisella tularensis is a highly infectious bacterium that causes the potentially lethal disease tularemia. This extremely virulent bacterium is able to replicate in the cytosolic compartments of infected macrophages. To invade macrophages and to cope with their intracellular environment, Francisella requires multiple virulence factors, which are still being identified. Proteins containing tetratricopeptide repeat (TPR)-like domains seem to be promising targets to investigate, since these proteins have been reported to be directly involved in virulence-associated functions of bacterial pathogens. Here, we studied the role of the FTS_0201, FTS_0778, and FTS_1680 genes, which encode putative TPR-like proteins in Francisella tularensis subsp. holarctica FSC200. Mutants defective in protein expression were prepared by TargeTron insertion mutagenesis. We found that the locus FTS_1680 and its ortholog FTT_0166c in the highly virulent Francisella tularensis type A strain SchuS4 are required for proper intracellular replication, full virulence in mice, and heat stress tolerance. Additionally, the FTS_1680-encoded protein was identified as a membrane-associated protein required for full cytopathogenicity in macrophages. Our study thus identifies FTS_1680/FTT_0166c as a new virulence factor in Francisella tularensis.
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