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，可以是扁桃体炎等轻微疾病以及更严重的侵入性感染的病原体。它有一个由碳水化合物组成的外囊，称为透明质酸。这种胶囊对殖民和感染至关重要。糖胺聚糖透明质酸（HA）是哺乳动物细胞的细胞外基质的组分。荚膜产生是GAS中已知的毒力因子，并且荚膜合成基因是宿主定殖所需的。有趣的是，大多数GAS基因组还编码至少四种被预测参与胶囊降解的基因：hylA，其编码分泌的透明质酸酶; hylA，其编码细胞质HA裂解酶;以及hylP 1和hylP 2，其与噬菌体相关，并且在DNA序列或蛋白质产物水平上与hylA或hylA不同源。有人建议GAS可以在不存在其他糖的情况下使用胶囊或宿主衍生的HA作为碳（营养）源。在体外，这个过程似乎依赖于hylA。其他三种HA降解酶的作用是什么？它们如何与中心碳代谢联系起来？病原体在感染过程中面临的挑战之一是缺乏重要的营养物质，如葡萄糖。当营养物质有限时，GAS可能会分解自己的胶囊来生存。这个BBSRC DTP项目旨在确定这种胶囊分解是如何发生的，以确定负责的关键酶，并研究这种胶囊回收如何有助于GAS对营养胁迫的适应性。该项目将产生知识，可能导致预防GAS感染或治疗现有感染的治疗方法。了解细菌如何处理复杂碳水化合物的代谢正在成为所有类型的人类-微生物相互作用的关键主题，从人类微生物群的维持到传染病的发展。

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.