Tissue injury including extracellular matrix (ECM) degradation is a hallmark of group A Streptococcal (GAS) skin infection. Hyaluronic acid, dermatan sulfate, heparin, heparan sulfate and chondroitin sulfate are glycosaminoglycans (GAGs) that are enriched in the cutaneous ECM and have important roles in bacterial colonisation and wound healing. The current study aimed to determine the specificity and affinity GAS M proteins for GAGs and assess the role of GAG binding in the interaction with skin cells. M proteins were found to interact with a range of GAGs, and, using site-directed mutagenesis, a novel arginine-arginine hyaluronic acid-binding motif in M53 protein was identified. Binding of GAGs by M protein was found to mediate attachment to the human keratinocyte cell line HaCat, and in the presence of M protein, Gags mediated wound healing was significantly delayed. These data suggest the GAG binding may contribute to GAS skin infection.