How does capsular polysaccharide degradation by Group A Streptococcus contribute to its survival?

A组化脓性链球菌(GAS)是一种人类病原体，可引起扁桃体炎等轻微疾病，也可引起更严重的侵袭性感染。它有一个外囊，由一种名为透明质酸的碳水化合物组成。这种胶囊对移居和感染至关重要。糖胺聚糖透明质酸(HA)是哺乳动物细胞外基质的一种成分。衣壳生产是赤霉菌已知的毒力因素，衣壳合成基因是寄主定植所必需的。有趣的是，大多数GAS基因组还编码至少四个基因，据预测参与胶囊降解：HylA，编码一种分泌型透明质酸酶；HySA，编码细胞质HA裂解酶；以及hylP1和hylP2，它们是与噬菌体相关的，在DNA序列或蛋白质产物水平上与Hyla或HySA不是同源的。有一种建议认为，在没有其他糖的情况下，GAS可以使用胶囊或宿主来源的HA作为碳(营养)来源。在体外，这一过程似乎依赖于Hyla。其他三种透明质酸降解酶的作用是什么，它们如何与中枢碳代谢联系起来？病原体在感染过程中面临的挑战之一是缺乏葡萄糖等重要营养物质。当营养有限时，气体可能会分解自己的胶囊以求生存。该BBSRC DTP项目旨在确定胶囊分解是如何发生的，确定负责的关键酶的特征，并调查这种胶囊回收如何有助于气体对营养胁迫的弹性。该项目将产生可能导致预防气体感染或治疗现有感染的治疗方法的知识。了解细菌如何处理复杂碳水化合物的新陈代谢，正在成为所有类型的人与微生物相互作用的关键主题，从维持人类微生物区系到发展传染病。

Group A Streptococcus pyogenes (GAS) is a human pathogen, which can be the causative agent of minor illnesses such as tonsillitis, as well as more serious invasive infections. It has an outer capsule composed of a carbohydrate called hyaluronic acid. This capsule is critical to colonisation and infection. The glycosaminoglycan hyaluronic acid (HA) is a component of the extracellular matrix of mammalian cells. Capsule production is a known virulence factor in GAS and capsule synthesis genes are required for host colonisation. Intriguingly, most GAS genomes also encode at least four genes that are predicted to participate in capsule degradation: hylA, which encodes a secreted hyaluronidase; hysA, which encodes a cytoplasmic HA lyase; and hylP1 and hylP2, which are bacteriophage associated and are not homologous to hylA or hysA at the level of DNA sequence or protein product. There is a proposal that GAS can use capsule- or host-derived HA as a carbon (nutrient) source in the absence of other sugars. In vitro, this process appears to depend on hylA. What are the roles of the other three HA-degrading enzymes and how do they link to central carbon metabolism? One of the challenges pathogens face during infection is lack of important nutrients like glucose. When nutrients are limited, GAS may break down its own capsule to survive. This BBSRC DTP project aims to establish how this capsule breakdown occurs, to characterise the key enzymes responsible, and to investigate how this capsule recycling contributes to GAS resilience to nutrient stress. This project will generate knowledge that could lead to therapeutics for prevention of GAS infection, or treatment of existing infections. Understanding how bacteria deal with the metabolism of complex carbohydrates is emerging as a key theme in all types of human-microbe interactions, from the maintenance of the human microbiota to the development of infectious diseases.