Role of NADase in virulence in experimental invasive group A streptococcal infection

Author(s): Bricker AL, Carey VJ, Wessels MR


Group A streptococci (GAS) produce several exoproteins that are thought to contribute to the pathogenesis of human infection. Two such proteins, streptolysin O (SLO) and NAD(+)-glycohydrolase (NADase), have been shown to interact functionally as a compound signaling toxin. When GAS are bound to the surface of epithelial cells in vitro, SLO forms pores in the cell membrane and delivers NADase to the epithelial cell cytoplasm. In vitro, intoxication of keratinocytes with NADase is associated with cytotoxic effects and induction of apoptosis; however, the importance of NADase during infection of an animal host has not been established. We employed isogenic GAS mutants to assess the contribution of NADase activity to GAS virulence in vivo using mouse models of invasive soft-tissue infection and septicemia. In both models, mutant GAS that lacked NADase activity were significantly attenuated for virulence compared with the isogenic wild-type parent, confirming an important role for NADase in the infection of a host animal. A double mutant lacking SLO and NADase activity had an intermediate virulence phenotype, consistent with the hypothesis that SLO evokes a protective innate immune response. We conclude that NADase and SLO together enhance GAS virulence in vivo.

Similar Articles

Bacterial meningitis in the United States in 1995

Author(s): Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, et al.

Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADP-ribosylating toxins

Author(s): Castagnini M,Picchianti M, Talluri E, Biagini M, Del Vecchio M, et al.

In silico identification of novel bacterial ADP-ribosyltransferases

Author(s): Masignani V,Balducci E, Serruto D, Veggi D, Aricò B, et al.

NarE: a novel ADP-ribosyltransferase from Neisseria meningitidis

Author(s): Masignani V,Balducci E, Di Marcello F, Savino S, Serruto D, et al.

Auto ADP-ribosylation of NarE, a Neisseria meningitidis ADP-ribosyltransferase, regulates its catalytic activities

Author(s): Picchianti M, Del Vecchio M, Di Marcello F, Biagini M, Veggi D, et al.

A fluorescent analog of nicotinamide adenine dinucleotide

Author(s): Barrio JR, Secrist JA 3rd, Leonard NJ

The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse

Author(s): Glowacki G,Braren R, Firner K, Nissen M, Kühl M, et al.

Activation of choleragen by thiol: protein disulfideoxidoreductase

Author(s): Moss J, Stanley SJ, Morin JE, Dixon JE

Iron transport systems in Neisseria meningitidis

Author(s): Perkins-Balding D, Ratliff-Griffin M, Stojiljkovic I