Diphosphopyridine Nucleotidase as an Extracellular Product of Streptococcal Growth and Its Possible Relationship to Leukotoxicity

Abstract

Among the extracellular growth products of hemolytic streptococci is a recently discovered protein that inhibits the oxidation of citrate, fumarate, and alpha-keto-glutarate by mitochondria (1). This protein has been purified and has been shown to catalyze specifically the cleavage of diphosphopyridine nucleotide (DPN) at the nicotinamide-ribose linkage (2).It was not known whether the release of diphosphopyridine nucleotidase (DPNase) accompanies growth of bacteria in general or whether it is uniquely associated with streptococci or with particular strains of streptococci. In order to answer this question we have examined for DPNase activity the culture supernates of diverse bacterial species and of a series of streptococcal strains. The findings suggest that DPNase is not commonly encountered as an extracellular growth product of bacteria excepting certain kinds of streptococci. Special attention has been given to streptococci in order to see whether capacity of these organisms to release DPNase is associated with other properties as serological type, pathogenicity, and leukotoxicity. Materials and MetkodsBacterial Strains.--Strains representative of bacterial species other than streptococci were obtained from the stock culture collection maintained in the New York laboratory for teaching purposes. A large number of streptococcal cultures of various groups and types were available in the two laboratories, and many of these had been obtained initially from Dr. Rebecca C. Lancefield. A considerable number of strains of streptococci known to have been associated

Contribution of Secreted NADase and Streptolysin O to the Pathogenesis of Epidemic Serotype M1 Streptococcus pyogenes Infections

“…The responsible agent was subsequently identified to be an extracellular NADase (SPN). 25 In 1957, by studying multiple streptococcal strains with and without NADase activity, Bernheimer et al 26 proposed a possible association between NADase production and streptococcal leukotoxicity. SLO, an oxygen-sensitive hemolysin, was first described by Neil and Mallory in 1928 and subsequently confirmed by Herbert and Todd in 1941.…”

The influence of the site of infection on the immune response to group A streptococci

“…The possibility that lipids, such as cholesterol, which are present in abundance in the skin may modify the antigenicity of streptolysin 0 in the same way that certain lipids modify both its hemolytic capacity and its cardiotoxic effects deserves consideration. Although there is no direct evidence to show that cholesterol or other skin lipids have the ability to modify the antigenicity of streptolysin 0, some difficulty in obtaining responses to intradermal injection of streptolysin 0 in experimental animals has been noted (30 (33). The present study confirms the tendency of Type 49 strains to produce more of this enzyme in vitro than most of the other types tested, but there was no evidence in this study that Type 49 infections produce higher antibody responses to this antigen than infections with other group A streptococci.…”

Studies on the Mode of Action of Diphtheria Toxin

“…Bernheimer et al (13) have demonstrated a striking correlation between the capacity of certaio strains of hemolytic streptococci to form NADase and their leukotoxicity. In this case, toxic activity is probably due directly to destruction of NAD by NADase released within the cell by phagocyted streptococci.…”