This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Buchanan, J. T.
Right arrow Articles by Nizet, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buchanan, J. T.
Right arrow Articles by Nizet, V.

 Previous Article  |  Next Article 

Infection and Immunity, October 2005, p. 6935-6944, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6935-6944.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Streptococcus iniae Phosphoglucomutase Is a Virulence Factor and a Target for Vaccine Development

John T. Buchanan,1* Jason A. Stannard,2 Xavier Lauth,2 Vaughn E. Ostland,2 Henry C. Powell,3 Mark E. Westerman,2 and Victor Nizet1

Departments of Pediatrics,1 Pathology, University of California, San Diego, School of Medicine, La Jolla, California 92093,3 Kent SeaTech Corporation, San Diego, California 921222

Received 14 December 2004/ Returned for modification 11 March 2005/ Accepted 2 June 2005

Streptococcus iniae represents a major health and economic problem in fish species worldwide. Random Tn917 mutagenesis and high-throughput screening in a hybrid striped bass (HSB) model of meningoencephalitis identified attenuated S. iniae mutants. The Tn917 insertion in one mutant disrupted an S. iniae homologue of a phosphoglucomutase (pgm) gene. Electron microscopy revealed a decrease in capsule thickness and cell wall rigidity, with {Delta}PGM mutant cells reaching sizes ~3-fold larger than those of the wild type (WT). The {Delta}PGM mutant was cleared more rapidly in HSB blood and was more sensitive to killing by cationic antimicrobial peptides including moronecidin from HSB. In vivo, the {Delta}PGM mutant was severely attenuated in HSB, as intraperitoneal challenge with 1,000 times the WT lethal dose produced only 2.5% mortality. Reintroduction of an intact copy of the S. iniae pgm gene on a plasmid vector restored antimicrobial peptide resistance and virulence to the {Delta}PGM mutant. In analysis of the aborted infectious process, we found that {Delta}PGM mutant organisms initially disseminated to the blood, brain, and spleen but were eliminated by 24 h without end organ damage. Ninety to 100% of fish injected with the {Delta}PGM mutant and later challenged with a lethal dose of WT S. iniae survived. We conclude that the pgm gene is required for virulence in S. iniae, playing a role in normal cell wall morphology, surface capsule expression, and resistance to innate immune clearance mechanisms. An S. iniae {Delta}PGM mutant is able to stimulate a protective immune response and may have value as a live attenuated vaccine for aquaculture.

* Corresponding author. Mailing address: University of California, San Diego, School of Medicine, 9500 Gilman Dr., Mail Code 0687, La Jolla, CA 92093. Phone: (858) 534-9760. Fax: (858) 534-5611. E-mail: jtbuchan{at}ucsd.edu.

Editor: V. J. DiRita

Infection and Immunity, October 2005, p. 6935-6944, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6935-6944.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Weiman, S., Dahesh, S., Carlin, A. F, Varki, A., Nizet, V., Lewis, A. L (2009). Genetic and biochemical modulation of sialic acid O-acetylation on group B Streptococcus: Phenotypic and functional impact. Glycobiology 19: 1204-1213 [Abstract] [Full Text]  
  • Paterson, G. K., Cone, D. B., Peters, S. E., Maskell, D. J. (2009). The enzyme phosphoglucomutase (Pgm) is required by Salmonella enterica serovar Typhimurium for O-antigen production, resistance to antimicrobial peptides and in vivo fitness. Microbiology 155: 3403-3410 [Abstract] [Full Text]  
  • Lowe, B. A., Miller, J. D., Neely, M. N. (2007). Analysis of the Polysaccharide Capsule of the Systemic Pathogen Streptococcus iniae and Its Implications in Virulence. Infect. Immun. 75: 1255-1264 [Abstract] [Full Text]  
  • Locke, J. B., Colvin, K. M., Datta, A. K., Patel, S. K., Naidu, N. N., Neely, M. N., Nizet, V., Buchanan, J. T. (2007). Streptococcus iniae Capsule Impairs Phagocytic Clearance and Contributes to Virulence in Fish. J. Bacteriol. 189: 1279-1287 [Abstract] [Full Text]  
  • Wang, C., Saldanha, M., Sheng, X., Shelswell, K. J., Walsh, K. T., Sobral, B. W. S., Charles, T. C. (2007). Roles of poly-3-hydroxybutyrate (PHB) and glycogen in symbiosis of Sinorhizobium meliloti with Medicago sp.. Microbiology 153: 388-398 [Abstract] [Full Text]  
  • Bizzini, A., Majcherczyk, P., Beggah-Moller, S., Soldo, B., Entenza, J. M., Gaillard, M., Moreillon, P., Lazarevic, V. (2007). Effects of {alpha}-phosphoglucomutase deficiency on cell wall properties and fitness in Streptococcus gordonii. Microbiology 153: 490-498 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»