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

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.