The clinical spectrum of patients with deficiency of Signal Transducer and Activator of Transcription-1.
ABSTRACT STAT-1 (Signal Transducer and Activator of Transcription-1) is a key signaling component of interferon gamma responses. We present long-term manifestations in siblings with a mutation in the STAT1 gene, which include invasive salmonellosis, recurrent severe respiratory syncytial virus pneumonitis, and hepatosplenic mycobacterial disease, and we summarize all other reported cases with STAT-1 deficiency.
Article: Identifying mechanisms by which Escherichia coli O157:H7 subverts interferon-γ mediated signal transducer and activator of transcription-1 activation.[show abstract] [hide abstract]
ABSTRACT: Enterohemorrhagic Escherichia coli serotype O157:H7 is a food borne enteric bacterial pathogen that causes significant morbidity and mortality in both developing and industrialized nations. E. coli O157:H7 infection of host epithelial cells inhibits the interferon gamma pro-inflammatory signaling pathway, which is important for host defense against microbial pathogens, through the inhibition of Stat-1 tyrosine phosphorylation. The aim of this study was to determine which bacterial factors are involved in the inhibition of Stat-1 tyrosine phosphorylation. Human epithelial cells were challenged with either live bacteria or bacterial-derived culture supernatants, stimulated with interferon-gamma, and epithelial cell protein extracts were then analyzed by immunoblotting. The results show that Stat-1 tyrosine phosphorylation was inhibited by E. coli O157:H7 secreted proteins. Using sequential anion exchange and size exclusion chromatography, YodA was identified, but not confirmed to mediate subversion of the Stat-1 signaling pathway using isogenic mutants. We conclude that E. coli O157:H7 subverts Stat-1 tyrosine phosphorylation in response to interferon-gamma through a still as yet unidentified secreted bacterial protein.PLoS ONE 01/2012; 7(1):e30145. · 4.09 Impact Factor