Document Detail


Genomic, proteomic, and transcriptomic analysis of virulent and avirulent Rickettsia prowazekii reveals its adaptive mutation capabilities.
MedLine Citation:
PMID:  20368341     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rickettsia prowazekii, the agent of epidemic typhus, is an obligate intracellular bacterium that is transmitted to human beings by the body louse. Several strains that differ considerably in virulence are recognized, but the genetic basis for these variations has remained unknown since the initial description of the avirulent vaccine strain nearly 70 yr ago. We use a recently developed murine model of epidemic typhus and transcriptomic, proteomic, and genetic techniques to identify the factors associated with virulence. We identified four phenotypes of R. prowazekii that differed in virulence, associated with the up-regulation of antiapoptotic genes or the interferon I pathway in the host cells. Transcriptional and proteomic analyses of R. prowazekii surface protein expression and protein methylation varied with virulence. By sequencing a virulent strain and using comparative genomics, we found hotspots of mutations in homopolymeric tracts of poly(A) and poly(T) in eight genes in an avirulent strain that split and inactivated these genes. These included recO, putative methyltransferase, and exported protein. Passage of the avirulent Madrid E strain in cells or in experimental animals was associated with a cascade of gene reactivations, beginning with recO, that restored the virulent phenotype. An area of genomic plasticity appears to determine virulence in R. prowazekii and represents an example of adaptive mutation for this pathogen.
Authors:
Yassina Bechah; Khalid El Karkouri; Oleg Mediannikov; Quentin Leroy; Nicolas Pelletier; Catherine Robert; Claudine Médigue; Jean-Louis Mege; Didier Raoult
Publication Detail:
Type:  Journal Article     Date:  2010-04-05
Journal Detail:
Title:  Genome research     Volume:  20     ISSN:  1549-5469     ISO Abbreviation:  Genome Res.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-04     Completed Date:  2010-08-23     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9518021     Medline TA:  Genome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  655-63     Citation Subset:  IM    
Affiliation:
Unit for Research on Emergent and Tropical Infectious Diseases (URMITE), Faculty of Medicine, Centre National de la Recherche Scientifique-Institut de Recherche pour le Développement, University of the Mediterranean, 13005 Marseille, France.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/CP001584; GEO/GSE15630;  GSE16123
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / genetics
Amino Acid Sequence
Animals
Bacterial Proteins / genetics,  metabolism
Base Sequence
Disease Models, Animal
Endothelial Cells / microbiology
Gene Expression Profiling*
Gene Expression Regulation
Gene Expression Regulation, Bacterial
Genomics*
Guinea Pigs
Humans
L Cells (Cell Line)
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Mutation*
Phenotype
Proteins / genetics,  metabolism
Proteomics*
Rickettsia prowazekii / genetics*,  metabolism,  pathogenicity*,  physiology
Typhus, Epidemic Louse-Borne / microbiology
Virulence
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Proteins
Comments/Corrections

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


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