Background: We identified Streptococcus pyogenes isolates with a mutation in the emm1 gene during an experimental infection. The mutation, resulting in the expression of a truncated, secreted M1 protein (XM), arose within a draining lymph node, during soft tissue infection. As M protein is considered an essential virulence factor, we sought to determine the factors which allowed XM to arise and persist.
Methods: A panel of isogenic emm1 strains were used; H584, H584XM, and H584∆emm1. These strains were assessed for their ability to cause experimental soft tissue and nasopharyngeal infections in mice. The fitness of the strains was compared in an intramuscular co-infection. Survival in whole human blood and whole mouse blood was also compared.
Results: Following soft tissue infection, XM caused greater systemic spread and was recovered in significantly higher numbers from the draining lymph node than its parent strain or H584∆emm1. XM was recovered in greater numbers from the infected hindlimb and draining lymph node following intramuscular co-infections than the parent strain. Contrastingly, cell wall-associated M1 protein was required to establish successful nasopharyngeal infection. Although XM was unable to survive well in human blood, net growth was increased in mouse blood compared to both other strains.
Conclusions: In this experimental system, M1 protein is not required for survival of GAS during invasive soft tissue infection but is necessary to establish nasopharyngeal colonisation. Loss of cell wall M protein coupled with expression of soluble M1 protein provides an advantage in the lymphatic niche and perhaps other immune privileged sites.