Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Role of streptokinase in early stages of group A streptococcus skin infection (#189)

Sergio Lizano 1 , Hemant Sabharwal 1 , Feng Luo 1 , Anhphan T Ly 1 , Farah K Tengra 1 , Candace N Rouchon 1 , John P Noto 1 , Debra E Bessen 1
  1. Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, USA

Streptokinase (Ska) is a critical virulence factor of group A streptococcus (GAS) that functions as a plasminogen activator, leading to plasmin formation and dissolution of fibrin clots. The three major structural forms of Ska correlate with GAS strains associated with different diseases. The goal of this study is to test the effects of different Ska forms on superficial skin infection by GAS, using a humanized mouse model for impetigo. The impetigo strain Alab49 expresses the plasminogen-binding protein (PAM) and Ska-2b, which act together to generate cell-bound plasmin activity. Deletion of the Ska-2b gene leads to loss of both cell-bound and fluid-phase plasmin activity, and a significant decrease in virulence at the skin at 3 d post-inoculation. In contrast, replacement of Ska-2b with Ska-1 on the Alab49 strain background yields both fluid-phase and cell-bound plasmin activity, and hypervirulence during the first 48 h of infection; the mean generation time at the skin for the Ska-1 chimera is less than half the time relative to WT. Although streptokinase has an established role as a "spreading factor" that facilitates invasion of deep tissue, data point to a critical role for streptokinase during the earliest stages of superficial skin infection. Overall, the findings are consistent with the idea that streptokinase acts to delay wound healing following minor trauma, thereby allowing the bacterium to establish a better foothold within the host.