Department of Molecular Biology and Biotechnology, The Florey Institute, University of Sheffield, Sheffield, UK.
Microbiology (Reading). 2018 Mar;164(3):242-250. doi: 10.1099/mic.0.000612. Epub 2018 Jan 25.
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.
DNases 在致病性链球菌中大量存在，大多数物种至少携带一种基因。然而，尽管这些酶广泛存在，但其在细胞外的作用仍然相对不明确。目前为止，已鉴定出 A 组链球菌（化脓性链球菌，S. pyogenes）的总共 8 种 DNase，它们的特征研究得最为透彻。已知其中 6 种与整合的噬菌体有关。两种是染色体编码的，其中一种是细胞壁锚定的。其他链球菌物种以及其他独特的 DNases 中也鉴定出了与噬菌体相关的和染色体编码的 S. pyogenes DNase 的同源物。链球菌 DNase 的一个主要作用似乎是破坏免疫细胞（如中性粒细胞）产生的细胞外陷阱，以捕获和杀死细菌。这些陷阱主要由可以被分泌和细胞壁锚定的链球菌 DNase 降解的 DNA 组成。DNase 还可以降低 TLR-9 信号转导以抑制免疫反应，并产生细胞毒性脱氧腺苷以限制吞噬作用。化脓性链球菌的上呼吸道感染模型表明，DNase 在增强感染和传播方面发挥作用，这可能是通过限制免疫反应或通过其他未知机制实现的。链球菌 DNase 也可能通过与其他微生物群落的通信、细菌杀伤和破坏竞争性生物膜或控制其自身生物膜的产生来相互作用。因此，DNase 对发病机制的贡献可能是广泛的，超出了对宿主免疫反应的直接干扰。
