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Two novel functions of hyaluronidase from Streptococcus agalactiae are enhanced intracellular survival and inhibition of proinflammatory cytokine expression.
- Source :
-
Infection and immunity [Infect Immun] 2014 Jun; Vol. 82 (6), pp. 2615-25. Date of Electronic Publication: 2014 Apr 07. - Publication Year :
- 2014
-
Abstract
- Streptococcus agalactiae is the causative agent of septicemia and meningitis in fish. Previous studies have shown that hyaluronidase (Hyl) is an important virulence factor in many Gram-positive bacteria. To investigate the role of S. agalactiae Hyl during interaction with macrophages, we inactivated the gene encoding extracellular hyaluronidase, hylB, in a clinical Hyl(+) isolate. The isogenic hylb mutant (Δhylb) displayed reduced survival in macrophages compared to the wild type and stimulated a significantly higher release of proinflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α), than the wild type in macrophages as well as in mice. Furthermore, only Hyl(+) strains could grow utilizing hyaluronic acid (HA) as the sole carbon source, suggesting that Hyl permits the organism to utilize host HA as an energy source. Fifty percent lethal dose (LD50) determinations in zebrafish demonstrated that the hylb mutant was highly attenuated relative to the wild-type strain. Experimental infection of BALB/c mice revealed that bacterial loads in the blood, spleen, and brain at 16 h postinfection were significantly reduced in the ΔhylB mutant compared to those in wild-type-infected mice. In conclusion, hyaluronidase has a strong influence on the intracellular survival of S. agalactiae and proinflammatory cytokine expression, suggesting that it plays a key role in S. agalactiae pathogenicity.
- Subjects :
- Analysis of Variance
Animals
Brain microbiology
Cells, Cultured
Colony Count, Microbial
Disease Models, Animal
Female
Fish Diseases microbiology
Gene Expression Regulation, Bacterial
Gene Silencing
Hyaluronoglucosaminidase genetics
Macrophages metabolism
Macrophages microbiology
Mice
Mice, Inbred BALB C
Spleen microbiology
Streptococcal Infections metabolism
Streptococcus agalactiae genetics
Streptococcus agalactiae growth & development
Streptococcus agalactiae pathogenicity
Zebrafish
Cytokines metabolism
Hyaluronoglucosaminidase physiology
Streptococcal Infections microbiology
Streptococcus agalactiae physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 82
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 24711564
- Full Text :
- https://doi.org/10.1128/IAI.00022-14