Research, Research Reports
Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly
Kristin Graumann1,3,#, Frieder Schaumburg1,4,#, Thomas F. Reubold2, Diana Hippe1, Susanne Eschenburg2 and Carsten G. K. Lüder1
Inhibition of programmed cell death pathways of mammalian cells often facilitates the sustained survival of intracellular microorganisms. The apicomplexan parasite Toxoplasma gondii is a master regulator of host cell apoptotic pathways. Here, we have characterized a novel anti-apoptotic activity of T. gondii. Using a cell-free cytosolic extract model, we show that T. gondii interferes with the activities of caspase 9 and caspase 3/7 which have been induced by exogenous cytochrome c and dATP. Proteolytic cleavage of caspases 9 and 3 is also diminished suggesting inhibition of holo-apoptosome function. Parasite infection of Jurkat T cells and subsequent triggering of apoptosome formation by exogenous cytochrome c in vitro and in vivo indicated that...
Exogenous folates stimulate growth and budding of Candida glabrata
Afsaneh Porzoor and Ian G. Macreadie
Folate, vitamin B9, is well recognized as being essential for cell growth. The utilization of folate is common to all cells, but the source of it may be quite different. This article reports a novel response of yeast to folates that may increase the utility of yeast as a model to study folate transport and signaling.
Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism
Camilla Ceccatelli Berti1, Cristina Dallabona1, Mirca Lazzaretti1, Sabrina Dusi2, Elena Tosi1, Valeria Tiranti2, Paola Goffrini1
Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. Yeast expressing a pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.
Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites
Carine F. Djuika1, Jaime Huerta-Cepas2, Jude M. Przyborski3, Sophia Deil1, Cecilia P. Sanchez1, Tobias Doerks2, Peer Bork2, Michael Lanzer1 and Marcel Deponte1
Horizontal gene transfer has emerged as a crucial driving force for the evolution of eukaryotes. This also includes Plasmodium falciparum and related economically and clinically relevant apicomplexan parasites, whose rather small genomes have been shaped not only by natural selection in different host populations but also by horizontal gene transfer following endosymbiosis. However, there is rather little reliable data on horizontal gene transfer between animal hosts or bacteria and apicomplexan parasites. Here we show that apicomplexan homologues of peroxiredoxin 5 (Prx5) have a prokaryotic ancestry and therefore represent a special subclass of Prx5 isoforms in eukaryotes. Using two different immunobiochemical approaches, we found that...
Two distinct and competitive pathways confer the cellcidal actions of artemisinins
Chen Sun#, Jian Li#, Yu Cao, Gongbo Long and Bing Zhou
The biological actions of artemisinin (ART), an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. This article concludes that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.
Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling
Viktor Scheidt1,#, André Jüdes1,#, Christian Bär1,2,#, Roland Klassen1 and Raffael Schaffrath1
The herein presented data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TOR-sensitive NCR branch via Gln3 misregulation.
Measurement of apoptosis by SCAN©, a system for counting and analysis of fluorescently labelled nuclei
Neta Shlezinger1,#, Elad Eizner1,2,#, Stas Dubinchik2, Anna Minz-Dub1, Rachel Tetroashvili1, Adi Reider1, Amir Sharon1
This work reports on a system for analyses of apoptosis-like programmed cell death in fungal hyphae that is composed of several modules, which enable automatic quantification of nuclei with chromatin condensation and DNA strand break in large datasets according to nuclei-associated fluorescent markers.
Rewiring yeast acetate metabolism through MPC1 loss of function leads to mitochondrial damage and decreases chronological lifespan
Ivan Orlandi1,2, Damiano Pellegrino Coppola2 and Marina Vai1,2
This work shows that MPC1-deficient cells make up for their impairment in mitochondrial pyruvate with a metabolic rewiring which involves several intermediates of the mitochondrially localized TCA cycle and the cytosolic glyoxylate shunt but ultimately results in a pro-aging process.
Airborne bacteria in show caves from Southern Spain
July 26, 2021
This study analyzes the factors conditioning the diversity of airborne bacteria recorded in three Andalusian show caves, subjected to different managements.
Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease
June 18, 2021
This study investigates the landscapes and alterations of mucosa-associated intestinal microbiota in patients with inflammatory bowel diseases, which cause chronic inflammation of the gut, including ulcerative colitis and Crohn’s disease.
Genome, transcriptome and secretome analyses of the antagonistic, yeast-like fungus Aureobasidium pullulans to identify potential biocontrol genes
June 8, 2021
This study highlights the value of a sequential approach starting with genome mining and consecutive transcriptome and secretome analyses in order to identify a limited number of potential target genes for detailed, functional analyses in Aureobasidium pullulans.
Proanthocyanidin-enriched cranberry extract induces resilient bacterial community dynamics in a gnotobiotic mouse model
April 29, 2021
This study investigates the effect of a water-soluble, proanthocyanidin-rich cranberry juice extract on the short-term dynamics of a human-derived bacterial community in a gnotobiotic mouse model.
Dry biocleaning of artwork: an innovative methodology for Cultural Heritage recovery?
April 15, 2021
This work proposes an innovative methodology based on applied biotechnology for the recovery of altered stonework: the "dry biocleaning", which envisages the use of dehydrated microbial cells without the use of free water or gel-based matrices.
Aeration mitigates endoplasmic reticulum stress in Saccharomyces cerevisiae even without mitochondrial respiration
March 31, 2021
This work demonstrates a scenario, in which aeration acts beneficially on Saccharmyces cerevisiae cells even under fermentative conditions.
A novel BR-SMAD is required for larval development in barber’s pole worm Haemonchus contortus
December 23, 2020
The herein presented results show a BMP-like receptor-regulated SMAD in Haemonchus contortus that is required for larval differentiation and underscore an adaptive functional repurposing of BMP-signaling in parasitic worms.
Nutrient sensing and cAMP signaling in yeast: G-protein coupled receptor versus transceptor activation of PKA
October 12, 2020
The herein presented work supports a model, in which nutrient transceptors are evolutionary ancestors of GPCRs, employing a more primitive direct signaling mechanism compared to the indirect cAMP second-messenger signaling mechanism used by GPCRs for activation of PKA.
Novobiocin inhibits membrane synthesis and vacuole formation of Enterococcus faecalis protoplasts
August 10, 2020
In this study Tsuchikado et al. show that DNA replication is crucial for plasma membrane biosynthesis and vacuole formation in Enterococcus faecalis protoplasts. Novobiocin inhibits DNA replication, blocking cell enlargement and vacuole formation. Extended treatment prevents re-enlargement after removal.