The enteropathogenic Escherichia coli-secreted protein EspZ inhibits host cell apoptosis.
نویسندگان
چکیده
The diarrheagenic pathogen enteropathogenic Escherichia coli (EPEC) limits the death of infected enterocytes early in infection. A number of bacterial molecules and host signaling pathways contribute to the enhanced survival of EPEC-infected host cells. EspZ, a type III secreted effector protein that is unique to EPEC and related "attaching and effacing" (A/E) pathogens, plays a role in limiting host cell death, but the precise host signaling pathways responsible for this phenotype are not known. We hypothesized that EspZ contributes to the survival of infected intestinal epithelial cells by interfering with apoptosis. Consistent with previous studies, scanning electron microscopy analysis of intestinal epithelial cells infected with an EPEC espZ mutant (ΔespZ) showed increased levels of apoptotic and necrotic cells compared to cells infected with the isogenic parent strain. Correspondingly, higher levels of cytosolic cytochrome c and increased activation of caspases 9, 7, and 3 were observed for ΔespZ strain-infected cells compared to wild-type (WT) EPEC-infected cells. Finally, espZ-transfected epithelial cells were significantly protected from staurosporine-induced, but not tumor necrosis factor alpha (TNF-α)/cycloheximide-induced, apoptosis. Thus, EspZ contributes to epithelial cell survival by mechanisms that include the inhibition of the intrinsic apoptotic pathway. The enhanced survival of infected enterocytes by molecules such as EspZ likely plays a key role in optimal colonization by A/E pathogens.
منابع مشابه
EspZ of Enteropathogenic and Enterohemorrhagic Escherichia coli Regulates Type III Secretion System Protein Translocation
UNLABELLED Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms tha...
متن کاملBreaking the Stereotype: Virulence Factor–Mediated Protection of Host Cells in Bacterial Pathogenesis
Bacterial pathogens have evolved extraordinary mechanisms to efficiently infect host organisms. A majority of these pathogens do so by delivering virulence factors into host cells, which act to dampen host defenses or utilize the host as a niche for replication. Although regulation of virulence factor expression by bacterial pathogens is a well known pathogenic mechanism [1], the concept of hos...
متن کاملNleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection.
The human pathogens enteropathogenic (EPEC) and enterohemorrhagic Escherichia coli and the related mouse pathogen Citrobacter rodentium subvert a variety of host cell signaling pathways via their plethora of type III secreted effectors, including triggering of an early apoptotic response. EPEC-infected cells do not develop late apoptotic symptoms, however. In this study we demonstrate that the ...
متن کاملEnteropathogenic Escherichia coli dynamically regulates EGFR signaling in intestinal epithelial cells.
The diarrheagenic pathogen enteropathogenic Escherichia coli (EPEC) dynamically modulates the survival of infected host intestinal epithelial cells. In the initial stages of infection, several prosurvival signaling events are activated in host cells. These include the phosphorylation of epidermal growth factor receptor (EGFR) and the consequent activation of the phosphatidylinositol-3 kinase/Ak...
متن کاملEnteropathogenic E. coli-induced barrier function alteration is not a consequence of host cell apoptosis.
Enteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen that perturbs intestinal epithelial function. Many of the alterations in the host cells are mediated by effector molecules that are secreted directly into epithelial cells by the EPEC type III secretion system. The secreted effector molecule EspF plays a key role in redistributing tight junction proteins and altering epithelia...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Infection and immunity
دوره 80 11 شماره
صفحات -
تاریخ انتشار 2012