The Differential Effect of Toxoplasma Gondii Infection on the Stability of BCL2-Family Members Involves Multiple Activities

Abstract

The regulation of mitochondrial permeability, a key event in the initiation of apoptosis is governed by the opposing actions of the pro- and anti-apoptotic members of the BCL2-family of proteins. The BCL2-family can be classified further based on the number of BCL-homology (BH) domains they encode. Pathogen mediated modulation of BCL2-family members play a significant role in their ability to affect the apoptotic pathways in the infected host cell. The protozoan parasite Toxoplasma gondii establishes a profound blockade of apoptosis noted by a requirement for host NFκB activity and correlating with the selective degradation of pro-apoptotic BCL2-family members. In this study, we explore the potential activities associated with the inherent stability of the anti-apoptotic BCL2 as well as the selective degradation of the pro-apoptotic proteins BAX, BAD, and BID. We find that multiple activities govern the relative stability of BCL2-family members suggesting a complex and balanced network of stability-enhancing and–destabilizing activities are perturbed by parasite infection. The data leave open the possibility for both parasite induced host activities as well as the direct consequence of parasite effectors in governing the relative levels of BCL2-proteins in the course of infection.

Temporal variations in patterns ofEscherichia colistrain diversity and antimicrobial resistance in the migrant Egyptian vulture

“…This variation could possibly be attributed to more than 400 wide-spread horizontally transferred genes coding β-lactamases in E. coli and permissibility of genome of E. coli to such genes, though chromosomal genes providing intrinsic resistance are not uncommon [49]. While many studies report ESBL in E. coli of wild species, the response of migration on cephalopsporin resistance determinants is poorly known [17]. …”

“…The near-absence of studies of the of E. coli in wild vertebrates in densely-populated countries is worrisome especially given the increased risk of wild species interacting with humans and domestic animals, and are urgently required [4]. In particular, documentation of the temporal and spatial patterns of antimicrobial drug resistance in different habitats and species in developing countries is essential to developing a cogent understanding of wildlife as a source of antimicrobial resistance [16,17]…”

Toxoplasma gondii Development of Its Replicative Niche: in Its Host Cell and Beyond

“…Consistent with these findings, Toxoplasma-infected cells show decreased levels of cleaved caspase-3, as well as of caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway) (57,59). A variety of potential upstream changes have also been noted, including increases in expression of inhibitor of apoptosis proteins (IAPs) (60) and of antiapoptotic members of the Bcl-2 family (45), activation of PI 3-kinase signaling (61), an NF-Bdependent degradation of proapoptotic Bcl-2 family members (BAX, BAD, and BID) (59,62), and upregulation and expression of STAT6-dependent specific serine protease inhibitors, including SERPIN B3 and B4, which are known to protect against tumor necrosis factor alpha (TNF-␣)-induced apoptosis (63).…”

Glucosylceramides are required for mycelial growth and full virulence in Penicillium digitatum

“…interacted with GlcCers and lead to the growth arrest of C. albicans and F. graminearum [5,10]. Although GlcCers were described as cell membrane constituents of mammal, plant and fungi [11], the structure of fungal GlcCers were remarkable distinct from their counterparts in animal cells [12], suggesting that GlcCers and GCS are the ideal targets for containing pathogenic fungi.…”