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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #218846
Title: Genome Sequence of Brucella abortus Vaccine Strain S19 Compared to Virulent Strains Yields Candidate Virulence Genes

Author
item CRASTA, O - VIRGINIA TECH
item FOLKERTS, O - VIRGINIA TECH
item FEI, Z - VIRGINIA TECH
item MANE, S - VIRGINIA TECH
item EVANS, C - VIRGINIA TECH
item MARTINO-CATT, S - VIRGINIA TECH
item Bricker, Betsy
item YU, G - VIRGINIA TECH
item DU, L - LIFE SCIENCES
item SOBRAL, B - VIRGINIA TECH

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/13/2008
Publication Date: 5/14/2008
Citation: Crasta, O.R., Folkerts, O., Fei, Z., Mane, S., Evans, C., Martino-Catt, S., Bricker, B.J., Yu, G., Du, L., Sobral, B.W. 2008. Genome Sequence of Brucella abortus Vaccine Strain S19 Compared to Virulent Strains Yields Candidate Virulence Genes. PLoS One. 3(5):e2193. Available: http:www.plosone.org/article/info:doi/10.1371/journal.pone.0002193.

Interpretive Summary: Brucellosis is a bacterial disease of livestock and humans throughout the world. It causes abortions in cattle and a disease called Undulent Fever in humans. Animals can be vaccinated for brucellosis with a weakened strain of the bacteria. There are two vaccine strains for animals, S19 and RB51. There are no vaccine strains approved for human use. It is unknown what causes strain S19 to be weaker but still strong enough to protect animals from infection with regular strains. In this paper, we determined the complete DNA sequence of vaccine strain S19, and associated the sequence data with known genes. The purpose of the reseach was to find genes that are different in S19 when compared to normal strains in the hope that they can explain why S19 works as a good vaccine. As a result of this work, a list was created of the most important genes discovered to be different in strain S19. Next, individual genes on this list will be further investigated in the future to see if they they play an important role in vaccine protection. Ultimately we hope this research will allow us to design new, safer and better vaccine strains that can be used in humans and animals.

Technical Abstract: We have applied pyrosequencing technology together with conventional sequencing to rapidly and comprehensively determine the complete genome sequence of the attenuated vaccine strain Brucella abortus S19. The main goal of this study was to identify possible virulence genes by systematic comparative analysis of the attenuated strain with the published genome sequences of two virulent and closely related strains of B. abortus, 9-941 and 2308. Pyrosequencing generated more than 800,000 sequence reads covering more than 20X of the S19 genome. The whole genome sequence was completed through additional targeted conventional sequencing of 139 gaps identified through alignment of the 172 contigs against the published whole genome sequence of B. abortus strain 9-941. The total length of the two S19 chromosomes was determined to be 2,122,487 and 1,161,449 bp. A total of 3133 genes were predicted and annotated by the PATRIC bioinformatics resource center and were used in pairwise comparison with those from the sequenced genomes of the two virulent strains. Differences at the nucleotide level were found in 284 genes. Amongst these, 51 genes of the attenuated strain were different from their respective homologs in both virulent strains but were identical amongst the virulent strains. Through integration of available data on published open reading frames (ORFs), we have identified a handful of genes that may be associated with virulence or loss thereof in B. abortus. Of particular importance is a gene that encodes, in the virulent strains, an outer membrane protein that appears to be involved in adhesion, invasion, and serum resistance. This paper discusses the characteristics of these genes, their possible relevance to virulence in the host species, and their potential merit for further development of vaccine strains designed for humans and animals.