Research, Research Articles

A versatile plasmid system for reconstitution and analysis of mammalian ubiquitination cascades in yeast

Rossella Avagliano Trezza1,#, Janny van den Burg1, Nico van den Oever1 and Ben Distel1,2

In this article Avagliano Trezza et al. describe a versatile vector system that allows the reconstitution of specific ubiquitination cascades in the model eukaryote Saccharomyces cerevisae (baker’s yeast) that provides a versatile tool to study complex post-translational modifications in a cellular setting.

Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae : biophysical mechanisms and implications for acetic acid tolerance

Lina Lindahl1, Samuel Genheden2, Fábio Faria-Oliveira1, Stefan Allard3, Leif A. Eriksson2, Lisbeth Olsson1, Maurizio Bettiga1,4

Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes.

Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin

Julia Ring1, Patrick Rockenfeller1, 3, Claudia Abraham1, Jelena Tadic1, Michael Poglitsch1, Katherina Schimmel1, 4, Julia Westermayer1, Simon Schauer1, Bettina Achleitner1, Christa Schimpel1, 5, Barbara Moitzi1, Gerald N. Rechberger1, 6, Stephan J. Sigrist7, 8, Didac Carmona-Gutierrez1, Guido Kroemer9, 10, 11, 12, 13, 14, 15, Sabrina Büttner1, 16, Tobias Eisenberg1, 2, Frank Madeo1, 2

This article indicates that spartin, a protein linked to hereditary spastic paraplegias, extends yeast lifespan and reduces age-related damage by associating with mitochondria and interacting with key metabolic proteins, implicating energy metabolism in its protective role during aging.

A genome-wide screen for FTY720-sensitive mutants reveals genes required for ROS homeostasis

Kanako Hagihara1, Kanako Kinoshita1, Kouki Ishida1, Shihomi Hojo1, Yoshinori Kameoka1, Ryosuke Satoh1, Teruaki Takasaki1 and Reiko Sugiura1

Fingolimod hydrochloride (FTY720) is an immune modulator for multiple sclerosis that also induces cancer cell apoptosis through reactive oxygen species generation, with a new study using fission yeast uncovering a gene network related to ROS homeostasis as a possible mechanism of FTY720's toxicity.

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica

Jannell V. Bazurto1, Stephen P. Dearth2, Eric D. Tague2, Shawn R. Campagna2 and Diana M. Downs1

In Salmonella enterica, aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. Data herein describe the use of metabolomics to identify the metabolic state of mutant strains and probe the underlying mechanisms used by AICAR to inhibit thiamine synthesis. The results obtained provide a cautionary tale of using metabolite concentrations as the only data to define the physiological state of a bacterial cell.

The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development

Cletus A. Wezena1, Romy Alisch1, Alexandra Golzmann2, Linda Liedgens1, Verena Staudacher1,3, Gabriele Pradel2 and Marcel Deponte1,3

In this study the authors demonstrate that, PfGlo1 and PfcGlo2 are dispensable during asexual blood-stage development while the loss of PfcGlo2 may induce the formation of transmissible gametocytes. These combined data show that PfGlo1 and PfcGlo2 are most likely not suited as targets for selective drug development against the malaria parasite Plasmodium falciparum.

Aminoglycoside resistance profile and structural architecture of the aminoglycoside acetyltransferase AAC(6’)-Im

Clyde A. Smith1, Monolekha Bhattacharya2, Marta Toth2, Nichole K. Stewart2 and Sergei B. Vakulenko2

AAC(6')-Im, a monofunctional acetyltransferase, imparts increased resistance to certain aminoglycosides compared to its bifunctional homolog AAC(6')-Ie, with structural studies revealing differences in substrate binding that explain the discrepancies in their enzymatic activity and resistance profiles.

Cross-species complementation of bacterial- and eukaryotic-type cardiolipin synthases

Petra Gottier1, Mauro Serricchio1, Rita Vitale2, Angela Corcelli2, and Peter Bütikofer1

This article shows that cardiolipin is crucial for cellular respiration and membrane integrity, with cardiolipin synthase enzymes like TbCLS in Trypanosoma brucei being potential drug targets due to their essential role in survival. The study demonstrates TbCLS's ability to restore cardiolipin production in yeast, highlighting the specificity and potential co-localization required for cardiolipin synthesis and remodeling, and underscoring the differences between eukaryotic and prokaryotic cardiolipin synthase mechanisms.

Identification of SUMO conjugation sites in the budding yeast proteome

Miguel Esteras1, I-Chun Liu1, Ambrosius P. Snijders2, Adam Jarmuz1 and Luis Aragon1

The authors present a proteomic study that mapped SUMO acceptor lysines in budding yeast, identifying 257 potential conjugation sites, including both known and novel substrates, and providing a significant resource for future research into the functional implications of SUMOylation in yeast.

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Clostridium scindens promotes gallstone formation by inducing intrahepatic neutrophil extracellular traps through CXCL1 produced by colonic epithelial cells

March 19, 2025

Through in vivo and in vitro experiments, we validated the reliability of C. scindens stimulating colonic epithelial cells to produce TLR2, activating the NF-κB signaling pathway, promoting CXCL1 expres-sion, and inducing intrahepatic neutrophil NETosis, which may be associated with gallstone formation.

Integrative Omics reveals changes in the cellular landscape of peroxisome-deficient pex3 yeast cells

February 20, 2025

To uncover the consequences of peroxisome deficiency, we compared Saccharomyces cerevisiae wild-type with pex3 cells, which lack peroxisomes, employing quantitative proteomics and transcriptomics technologies.

A complex remodeling of cellular homeostasis distinguishes RSV/SARS-CoV-2 co-infected A549-hACE2 expressing cell lines

October 8, 2024

Given the common tropism of SARS-CoV-2 and RSV, and the unclear consequences of their mutual influence, we developed an in vitro lung epithelial cell model to study the molecular mechanisms and cellular pathways modulated in viral co-infection.

RidA proteins contribute to fitness of S. enterica and E. coli by reducing 2AA stress and moderating flux to isoleucine biosynthesis

October 4, 2024

This study solidifies the established role of RidA in removing 2AA, while also presenting evidence for a role of RidA in enhancing flux towards isoleucine biosynthesis in E. coli. Overall, these data emphasize that metabolic networks can generate distinct responses to perturbation, even when the individual components are conserved.

Fecal gelatinase does not predict mortality in patients with alcohol-associated hepatitis

August 26, 2024

This study aimed to investigate the significance of fecal gelatinase on clinical outcomes in patients with alcohol-associated hepatitis. In conclusion, in our cohort, fecal gelatinase does not predict mortality and does not indicate higher disease severity in patients with alcohol-associated hepatitis.

Promoter methylation and increased expression of PD-L1 in patients with active tuberculosis

July 29, 2024

The PD-1/PD-L1 pathway plays a pivotal role in T cell activity and is involved in the pathophysiology of tuberculosis. Here we show that PD-L1 expression is increased in patients with active tuberculosis and is correlated with treatment outcomes.

Quantification methods of Candida albicans are independent irrespective of fungal morphology

July 26, 2024

Our study demonstrated that the quantification methods of C. albicans (cells/mL, CFU/mL, and vPCR) did not agree, regardless of the fungal morphology/growth, even though a significant and strong correlation is observed.

Pathogenic Escherichia coli change the adhesion between neutrophils and endotheliocytes in the experimental bacteremia model

July 22, 2024

In this work, we have demonstrated that in the model of experimental septicemia there is a disruption of adhesion contacts between neutrophils and endothelial cells, manifested by a decrease in adhesion force and work upon exposure to E. coli.

Arsenite treatment induces Hsp90 aggregates distinct from conventional stress granules in fission yeast

July 19, 2024

Given the conserved role of Hsp90 as a molecular chaperone protein, our findings presented in this study may suggest a novel type of arsenite-induced biological condensates, wherein Hsp90 plays a key role in maintaining its integrity.

Expansion of metabolically labelled endocytic organelles and cytoskeletal cell structures in Giardia lamblia using optimised U- ExM protocols

June 21, 2024

Understanding cellular ultrastructure is tightly bound to microscopic resolution and the ability to identify individual components at that resolution. In this study we demonstrate mostly isotropic 4.5-fold expansion of several different compartments in Giardia cells and present an optimised, shortened, and modular protocol that can be swiftly adjusted to the investigators needs.

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