PUBLICATION
First Streptococcus pyogenes Signature-Tagged Mutagenesis Screen Identifies Novel Virulence Determinants
- Authors
- Kizy, A.E., and Neely, M.N.
- ID
- ZDB-PUB-090227-9
- Date
- 2009
- Source
- Infection and Immunity 77(5): 1854-1865 (Journal)
- Registered Authors
- Neely, Melody N.
- Keywords
- none
- MeSH Terms
-
- Animals
- DNA Transposable Elements
- Fasciitis, Necrotizing/microbiology
- Mutagenesis, Insertional/methods*
- Streptococcal Infections/microbiology
- Streptococcus pyogenes/genetics*
- Streptococcus pyogenes/pathogenicity*
- Virulence
- Virulence Factors/genetics*
- Zebrafish
- PubMed
- 19223485 Full text @ Infect. Immun.
Citation
Kizy, A.E., and Neely, M.N. (2009) First Streptococcus pyogenes Signature-Tagged Mutagenesis Screen Identifies Novel Virulence Determinants. Infection and Immunity. 77(5):1854-1865.
Abstract
The virulence of bacterial pathogens is a complex process that requires the dynamic expression of many genes in order to invade and circumvent host defenses, as well as to proliferate in vivo. In this study, we employed a large-scale screen, signature-tagged mutagenesis (STM), to identify Streptococcus pyogenes virulence genes important for pathogenesis within the host. Approximately 1200 STM mutants were created and screened through the zebrafish infectious disease model. The transposon insertion site was identified for 29 of the 150 mutants that were considered attenuated for virulence. Previously reported streptococcal virulence genes, such as mga, hasA, amrA, smeZ and two genes of the sil locus, were identified, confirming the utility of the model for revealing genes important for virulence. Multiple genes not previously implicated in virulence were also identified, including putative transporters, hypothetical cytosolic proteins and macrolide efflux pumps. The STM mutant strains display varying levels of attenuation and multiple separate insertions were identified either in the same gene or locus, suggesting that those factors are important for this type of acute, invasive infection. We examined further two such genes, silB and silC of a putative quorum sensing regulon, and determined them to be significant virulence factors in our model of necrotizing fasciitis. silC promoter expression was examined under various in vitro conditions, as well as in zebrafish tissues, and found to be differentially induced. This study provides a unique investigation of S. pyogenes factors required for a successful invasive infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping