Open AccessMolecular architecture of Streptococcus pneumoniae surface thioredoxin‐fold lipoproteins crucial for extracellular oxidative stress resistance and maintenance of virulence
Author(s) -
Saleh Malek,
Bartual Sergio G.,
Abdullah Mohammed R.,
Jensch Inga,
Asmat Tauseef M.,
Petruschka Lothar,
Pribyl Thomas,
Gellert Manuela,
Lillig Christopher H.,
Antelmann Haike,
Hermoso Juan A.,
Hammerschmidt Sven
Publication year - 2013
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201202435
Subject(s) - methionine sulfoxide reductase , virulence , streptococcus pneumoniae , microbiology and biotechnology , thioredoxin , biology , oxidative stress , pathogen , phagocytosis , biochemistry , methionine , gene , amino acid , antibiotics
The respiratory pathogen Streptococcus pneumoniae has evolved efficient mechanisms to resist oxidative stress conditions and to displace other bacteria in the nasopharynx. Here we characterize at physiological, functional and structural levels two novel surface‐exposed thioredoxin‐family lipoproteins, Etrx1 and Etrx2. The impact of both Etrx proteins and their redox partner methionine sulfoxide reductase Sp MsrAB2 on pneumococcal pathogenesis was assessed in mouse virulence studies and phagocytosis assays. The results demonstrate that loss of function of either both Etrx proteins or Sp MsrAB2 dramatically attenuated pneumococcal virulence in the acute mouse pneumonia model and that Etrx proteins compensate each other. The deficiency of Etrx proteins or Sp MsrAB2 further enhanced bacterial uptake by macrophages, and accelerated pneumococcal killing by H 2 O 2 or free methionine sulfoxides (MetSO). Moreover, the absence of both Etrx redox pathways provokes an accumulation of oxidized Sp MsrAB2 in vivo . Taken together our results reveal insights into the role of two extracellular electron pathways required for reduction of Sp MsrAB2 and surface‐exposed MetSO. Identification of this system and its target proteins paves the way for the design of novel antimicrobials.