Document Detail


An atypical riboflavin pathway is essential for Brucella abortus virulence.
MedLine Citation:
PMID:  20195542     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Brucellosis is a worldwide zoonosis that affects livestock and humans and is caused by closely related Brucella spp., which are adapted to intracellular life within cells of a large variety of mammals. Brucella can be considered a furtive pathogen that infects professional and non-professional phagocytes. In these cells Brucella survives in a replicative niche, which is characterized for having a very low oxygen tension and being deprived from nutrients such as amino acids and vitamins. Among these vitamins, we have focused on riboflavin (vitamin B2). Flavin metabolism has been barely implicated in bacterial virulence. We have recently described that Brucella and other Rhizobiales bear an atypical riboflavin metabolic pathway. In the present work we analyze the role of the flavin metabolism on Brucella virulence. Mutants on the two lumazine synthases (LS) isoenzymes RibH1 and RibH2 and a double RibH mutant were generated. These mutants and different complemented strains were tested for viability and virulence in cells and in mice. In this fashion we have established that at least one LS must be present for B. abortus survival and that RibH2 and not RibH1 is essential for intracellular survival due to its LS activity in vivo. In summary, we show that riboflavin biosynthesis is essential for Brucella survival inside cells or in mice. These results highlight the potential use of flavin biosynthetic pathway enzymes as targets for the chemotherapy of brucellosis.
Authors:
Hernán Ruy Bonomi; María Inés Marchesini; Sebastián Klinke; Juan E Ugalde; Vanesa Zylberman; Rodolfo A Ugalde; Diego J Comerci; Fernando Alberto Goldbaum
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-25
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-02     Completed Date:  2010-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e9435     Citation Subset:  IM    
Affiliation:
Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bacterial Proteins / genetics,  metabolism*
Biosynthetic Pathways*
Blotting, Western
Brucella abortus / genetics,  metabolism*,  pathogenicity
Brucellosis / microbiology
Cell Line
Female
Genetic Complementation Test
Hela Cells
Humans
Isoenzymes / genetics,  metabolism
Lysosome-Associated Membrane Glycoproteins / metabolism
Macrophages / cytology,  metabolism,  microbiology
Mice
Mice, Inbred BALB C
Microbial Viability
Multienzyme Complexes / genetics,  metabolism
Mutation
Riboflavin / biosynthesis*
Virulence
Grant Support
ID/Acronym/Agency:
R01AI078891-01/AI/NIAID NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Isoenzymes; 0/Lamp1 protein, mouse; 0/Lysosome-Associated Membrane Glycoproteins; 0/Multienzyme Complexes; 83-88-5/Riboflavin; 89287-46-7/6,7-dimethyl-8-ribityllumazine synthase
Comments/Corrections

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