Streptococcus pneumoniae surface-exposed thioredoxin-like proteins that are involved in defence against oxidative stress

22 de Mayo de 2013

 Streptococcus pneumoniae surface-exposed thioredoxin-like proteins that are involved in defence against oxidative stress
In this work we characterize at physiological and structural levels two novel surface-exposed lipoproteins with thioredoxin-like fold. The impact of the Etrx proteins on pneumococcal pathogenesis was assessed in mouse virulence studies and phagocytosis assays. Our studies indicate that loss of function of both Etrx proteins dramatically attenuated pneumococcal virulence in the acute pneumonia model, while no effect was shown in the sepsis model. The pneumonia model further indicated that Etrx2 compensates for the absence of Etrx1 and vice versa. In addition, the deficiency of both Etrx proteins enhanced bacterial uptake by macrophages, oxidative damage of proteins, and accelerated pneumococcal killing by H2O2. We thus provide insights into the complete extracellular oxidative-stress-resistance system critical for reduction of surface-exposed proteins. Identification of this system and their target proteins pave the way for the design of novel antimicrobials.