Genetic dissection of streptococcus pyogenes induced macrophage death

  • Lengeling, Andreas (Principal Investigator)

Project Details

Description

Group A streptococcus (GAS; Streptococus pyogenes), is an important pathogen that can cause diseases of various severity in humans ranging from mild to life-threatening infections. Streptococcal toxic shock syndrome (STSS) is the most severe manifestation of invasive GAS infections. Clinical symptoms of STSS include hypotension, multiple organ failure and are associated with high mortality rate (30%-80%) despite prompt antibiotic therapy. The objective of this study is to identify genes associated with the development of septic shock in a murine model of GAS infection. In collaboration with the laboratory of Dr. Eva Medina (HZI, Braunschweig) we have previously shown that different strains of mice differ markedly in their susceptibility to GAS infection (Medina et al., 2001; Medina and Lengeling, 2005). Resistant strains, such as BALB/c are able to rapidly clear the infection. In contrast, susceptible mouse strains (e.g. C3H/HeN) are unable to control the infection. In these mice bacteria are rapidly multiplying in infected organs, causing overshooting inflammatory responses and sepsis. Using genetic linkage studies we found that resistance / susceptibility to GAS infection is a multigenic trait. Genome screens identified quantitative trait loci (QTLs) on mouse chromosomes 2, 7, and 17 (Goldmann et al., 2005). Currently, we are embarking on the genetic characterisation of the QTL located on proximal mouse chromosome 17 using congenic strains, gene expression profiling and high resolution SNP mapping. We are also investigating the underlying mechanisms of Streptococcus induced macrophage cell death which contributes to host susceptibility against GAS infections.
StatusFinished
Effective start/end date1/04/1031/05/12

Funding

  • UK-based charities: £289,505.00