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
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
Externí odkaz: