Streptococcus iniae M-like protein contributes to virulence in fish and is a target for live attenuated vaccine development
Autor: | Ramy K. Aziz, John T. Buchanan, Mike R. Vicknair, Jeffrey B. Locke, Victor Nizet |
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Rok vydání: | 2008 |
Předmět: |
Virulence Factors
Mutant Molecular Sequence Data lcsh:Medicine Virulence Locus (genetics) Microbiology/Innate Immunity Biology Infectious Diseases/Bacterial Infections 03 medical and health sciences Open Reading Frames Microbiology/Applied Microbiology Immunology/Immunity to Infections Endopeptidases Animals Biotechnology/Applied Microbiology Streptococcus iniae Amino Acid Sequence lcsh:Science Adhesins Bacterial Gene Alleles Phylogeny 030304 developmental biology Regulator gene Genetics 0303 health sciences Vaccines Multidisciplinary Attenuated vaccine Models Genetic Sequence Homology Amino Acid 030306 microbiology lcsh:R Fishes Computational Biology Streptococcus Genetics and Genomics/Bioinformatics biology.organism_classification Genetics and Genomics/Microbial Evolution and Genomics 3. Good health Bacterial adhesin Gene Expression Regulation lcsh:Q Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 3, Iss 7, p e2824 (2008) |
ISSN: | 1932-6203 |
Popis: | Background Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI). Methodology/Principal Findings S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the ΔsimA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development. Conclusions/Significance Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine. |
Databáze: | OpenAIRE |
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