DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection (Nat Med, 2007, 13:981-985)

報告日期: 2007/10/16
報告時間: 15:10/16:00
報告學生: 劉宜芳
講評老師: 林以行

DNase Sda1 provides selection pressure for a switch to invasive group A streptococcal infection

Walker MJ et al., 2007, Nature Medicine, 13(8):981-5

CommentatorDr. Yee-Shin Lin  

SpeakerYi-Fang Liu  


Place602:00, 16 Nov. 2007



Group A streptococci (GAS) cause a wide variety of human diseases ranging from mild infections such as pharyngitis and impetigo to severe diseases as streptococcal toxic shock syndrome and necrotizing fasciitis. The invasive diseases causing high mortality have related to the emergence of M1 clone dominantly.1 A two-component regulator, covRS, is known to negatively control several virulence genes and the mutation is found to link with the invasive infection. Moreover, it is common to find decreased speB and increased sda1 (encode a DNase) expression in invasive infection.2 To elucidate the selection pressure for the rapid loss of SpeB expression in vivo, 5448AP, an isogenic animal-passaged SpeB-negative covRS mutant from a human M1 GAS isolate, was analyzed. Comparing to 5448 wild-type, 5448AP abrogated the SpeB activity but increased M1 protein, streptokinase and plasmin activity, which lead to higher mortality and systemic infection. Moreover, the expression of sda1 was increased in 5448 in vivo. The ability of DNase activity, clearance of neutrophil extracellular traps and resistance to neutrophil killing was increased in 5448AP but decrease in the sda1 isogenic mutant of 5448. The expression of speB was abolished in the sda1 mutant and restored in complementation strain. It is concluded that sda1 may provide the selection pressure in vivo to turn off the speB expression and can lead to resist the neutrophil killing and disseminated the systemic infection.


1.   Cunningham, M. W. (2000). Pathogenesis of group A streptococcal infections. Clin Microbiol Rev 13, 470-511.

2.   Sumby, P., Whitney, A. R., Graviss, E. A., DeLeo, F. R. & Musser, J. M. (2006). Genome-wide analysis of group a streptococci reveals a mutation that modulates global phenotype and disease specificity. PLoS Pathog 2, e5.