Two novel functions of hyaluronidase from Streptococcus agalactiae are enhanced intracellular survival and inhibition of proinflammatory cytokine expression.
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.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Zhaofei
Z
Wang
Changming
C
Guo
Yannan
Y
Xu
Guangjin
G
Liu
Chengping
C
Lu
Yongjie
Y
Liu
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000382:microbiology; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005393:Fish Diseases / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D020868:Gene Silencing; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000382:microbiology; D013290:Streptococcal Infections / Q000378:metabolism / Q000382:microbiology*; D013292:Streptococcus agalactiae / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D015027:Zebrafish
D016207:Cytokines; D006821:Hyaluronoglucosaminidase