The DNases of pathogenic Lancefield streptococci

Abstract

DNases are abundant among the pathogenic streptococci, with most species harbouring genes for at least one. Despite their prevalence, however, the role for these extracellular enzymes is still relatively unclear. The DNases of the Lancefield group A Streptococcus, S. pyogenes are the best characterized, with a total of eight DNase genes identified so far. Six are known to be associated with integrated prophages. Two are chromosomally encoded, and one of these is cell-wall anchored. Homologues of both prophage-associated and chromosomally encoded S. pyogenes DNases have been identified in other streptococcal species, as well as other unique DNases. A major role identified for streptococcal DNases appears to be in the destruction of extracellular traps produced by immune cells, such as neutrophils, to ensnare bacteria and kill them. These traps are composed primarily of DNA which can be degraded by the secreted and cell-wall-anchored streptococcal DNases. DNases can also reduce TLR-9 signalling to dampen the immune response and produce cytotoxic deoxyadenosine to limit phagocytosis. Upper respiratory tract infection models of S. pyogenes have identified a role for DNases in potentiating infection and transmission, possibly by limiting the immune response or through some other unknown mechanism. Streptococcal DNases may also be involved in interacting with other microbial communities through communication, bacterial killing and disruption of competitive biofilms, or control of their own biofilm production. The contribution of DNases to pathogenesis may therefore be wide ranging and extend beyond direct interference with the host immune response.

Keywords: DNases; Streptococcus pyogenes; neutrophil extracellular traps.