Research, Research Articles

Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection

Tiago Monteiro-Brás1,2,3, Jordan Wesolowski1 and Fabienne Paumet1

This study reveals that the plasma membrane SNARE proteins SNAP-23 and Syntaxin 4 are crucial for Chlamydia trachomatis development by regulating lipid droplet homeostasis and supporting the formation of infectious progeny within host cells.

Yeast can express and assemble bacterial secretins in the mitochondrial outer membrane

Janani Natarajan1, Anasuya Moitra1, Sussanne Zabel1,§, Nidhi Singh2, Samuel Wagner2,3 and Doron Rapaport1

Secretins, essential components of bacterial secretion systems, can be expressed in yeast and show differential dependencies on mitochondrial import and assembly factors for membrane integration, suggesting diverse pathways for their assembly into the bacterial outer membrane.

Metabolic reprogramming of Salmonella infected macrophages and its modulation by iron availability and the mTOR pathway

Julia Telser1,2,#, Chiara Volani1,3,#, Richard Hilbe1,2, Markus Seifert1,2, Natascha Brigo1, Giuseppe Paglia4 and Günter Weiss1,2

This article shows that iron plays a critical role in both the immune response and metabolic reprogramming of macrophages during infection, influencing the TCA cycle and mTOR pathway, with implications for the growth of intracellular bacteria like Salmonella.

Type II-Metacaspases are involved in cell stress but not in cell death in the unicellular green alga Dunaliella tertiolecta

M. Teresa Mata1,&, Armando Palma1, Candela García-Gómez1,#, María López-Parages1, Víctor Vázquez1, Iván Cheng-Sánchez2, Francisco Sarabia2, Félix López-Figueroa1, Carlos Jiménez1 and María Segovia1

This article shows that in the green alga Dunaliella tertiolecta, Type-II metacaspases are involved in the stress response to ultraviolet radiation but are not linked to cell death, suggesting their role in survival strategies under stressful environmental conditions.

Transcriptomic and chemogenomic analyses unveil the essential role of Com2-regulon in response and tolerance of Saccharomyces cerevisiae to stress induced by sulfur dioxide

Patrícia Lage1,2, Belém Sampaio-Marques3,4, Paula Ludovico3,4, Nuno P. Mira5 and Ana Mendes-Ferreira1,2

This article shows that in the presence of sulfur dioxide (SO2), the transcription factor Com2 plays a critical role in the tolerance and response of Saccharomyces cerevisiae, affecting the expression of a majority of SO2-activated genes and contributing to the protection against stress induced by SO2 at an enologically relevant pH.

Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae

Yukio Mukai1, Yuka Kamei1, Xu Liu1, Shan Jiang1, Yukiko Sugimoto2, Noreen Suliani binti Mat Nanyan2, Daisuke Watanabe2 and Hiroshi Takagi2

This article shows that intracellular proline levels in the budding yeast Saccharomyces cerevisiae are correlated with its replicative lifespan, suggesting a protective role of proline against cellular senescence due to various stresses.

Network dynamics of the yeast methyltransferome

Guri Giaever1, Elena Lissina1 and Corey Nislow1

This article presents a systematic genetic analysis of methyltransferases (MTases) under normal and stress conditions, uncovering the complex and adaptive nature of the methyltransferome and discovering a potential connection between phospholipid methylation and histone methylation, suggesting interplay between lipid homeostasis and epigenetic regulation.

Functional link between mitochondria and Rnr3, the minor catalytic subunit of yeast ribonucleotide reductase

Isaac Corcoles-Saez1, Jean-Luc Ferat2, Michael Costanzo3, Charles M. Boone3 and Rita S. Cha1

This article shows that the carbon source affects the abundance of ribonucleotide reductase (RNR) subunits in yeast, with a novel Mec1 signaling axis regulating Rnr3 independently of known DNA damage response pathways, and reveals Rnr3's unexpected role in mitochondrial function.

Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release

Alexandre Légiot1, Claire Céré1, Thibaud Dupoiron1, Mohamed Kaabouni1, Nadine Camougrand1 and Stéphen Manon1

This study investigated the role of Mitochondria-Associated Membranes (MAMs) in the regulation of apoptosis by analyzing the localization and function of the pro-apoptotic protein Bax in yeast, finding that disruption of MAMs by deletion of the MDM34 gene affects Bax's mitochondrial localization and the release of cytochrome c.

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A modular cloning (MoClo) toolkit for reliable intracellular protein targeting in the yeast Saccharomyces cerevisiae

February 28, 2023

In this study, we describe an advanced Molecular cloning toolkit that is designed for the baker’s yeast Saccharomyces cerevisiae and optimized for the targeting of proteins of interest to specific cellular compartments.

The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes

January 27, 2023

By CRISPR/Cas9 knockout and biophysical analysis, we show here that the invariant surface glycoprotein 75 directly binds the the century-old drug suramin and mediates uptake of additional naphthol-related compounds, making this glycoprotein a conduit for entry of at least one structural class of trypanocidal compounds.

The first taxonomic and functional characterization of human CAVD-associated microbiota

January 13, 2023

Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process. In this study, we aimed to investigate and characterize the presence of valvular microbiota and the associated immune response in human CAV samples originating from two European populations.

Cellular cholesterol licenses Legionella pneumophila intracellular replication in macrophages

December 6, 2022

Host membranes are inherently critical for niche homeostasis of vacuolar pathogens such as Legionella. One membrane component that is often subverted by vacuolar bacteria is cholesterol. We provide experimental evidence that cellular cholesterol promotes L. pneumophila replication within a membrane bound organelle in infected macrophages.

DadY (PA5303) is required for fitness of Pseudomonas aeruginosa when growth is dependent on alanine catabolism

November 22, 2022

Pseudomonas aeruginosa inhabits diverse environmental niches that can have varying nutrient composition. The ubiquity of this organism is facilitated by a metabolic strategy that preferentially utilizes low-energy, non-fermentable organic acids, such as amino acids, rather than the high-energy sugars preferred by many other microbes. The amino acid alanine is among the preferred substrates of P. aeruginosa. The dad locus encodes the constituents of the alanine catabolic pathway of P. aeruginosa. Physiological roles for DadR (AsnC-type transcriptional activator), DadX (alanine racemase), and DadA (D-amino acid dehydrogenase) have been defined in this pathway. An additional protein, PA5303, is encoded in the dad locus in P. aeruginosa. PA5303 is a member of the ubiquitous Rid protein superfamily and is designated DadY based on the data presented herein. (...)

Multiple genome analysis of Candida glabrata clinical isolates renders new insights into genetic diversity and drug resistance determinants

October 13, 2022

The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as Candida species. Candida glabrata ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as PDR1 (azole resistance) or FKS1/2 (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of C. glabrata drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The(...)

Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles

July 15, 2022

Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between membranes and contribute to longevity in different manners. We previously found that a 2-fold up-regulation of Osh6, one of seven yeast oxysterol-binding proteins, remedies vacuolar morphology defects in mid-aged cells, partly down-regulates the target of rapamycin complex 1 (TORC1), and increases the replicative lifespan. At the molecular level, Osh6 transports phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI4P) between the endoplasmic reticulum (ER) and the plasma membrane (PM). To decipher how an ER-PM working protein controls vacuolar morphology, we tested genetic interactions between OSH6 and DRS2, whose protein flips PS from the lumen to the cytosolic side of the Golgi, the organelle between ER and vacuoles in many pathways. Up-regulated (...)

Air- and dustborne fungi in repositories of the National Archive of the Republic of Cuba

April 1, 2022

This study has as objectives to determine the concentration and diversity of the air- and dustborne mycobiota in seven National Archive of the Republic of Cuba repositories, and to assess the potential risk of biodeterioration that iso-lated taxa may have. In the indoor and outdoor environmental microbiological samplings a SAS biocollector was used and the indoor/outdoor (I/O) ratio was determined for each repository. The settled dust was collected during six months. Sørensen's coefficient of similarity (QS) was calculated to compare the isolated taxa among the three studied niches (indoor air, dust, outdoor air). The biodegradation potential of the isolated taxa was determined by semi-quantitative tests. The concentrations in the air of repositories with natural cross-ventilation ranged from 225.2-750.3 CFU m-3, while in the Map library with air-conditioning (...)

Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability

January 31, 2022

Topoisomerase 1 (Top1) removes transcription-associated helical stress to suppress G4-formation and its induced recombination at genomic loci containing guanine-run containing sequences. Interestingly, Top1 binds tightly to G4 structures, and its inhibition or depletion can cause elevated instability at these genomic loci. Top1 is targeted by the widely used anti-cancer chemotherapeutic camptothecin (CPT) and its derivatives, which stabilize Top1 covalently attached on a DNA nick and prevent the re-ligation step. Here we investigated how CPT-resistance conferring Top1 mutants, which emerge in cancer patients and cells treated with CPT, affect G4-induced genomic instability in S. cerevisiae. We found that Top1 mutants form stable complexes with G4 DNA and that expression of Top1 cleavage-defective mutants but not a DNA-binding-defective (...)

Chromosome-condensed G1 phase yeast cells are tolerant to desiccation stress

November 26, 2021

The budding yeast Saccharomyces cerevisiae is capable of surviving extreme water loss for a long time. However, less is known about the mechanism of its desiccation tolerance. In this study, we revealed that in an exponential culture, all desiccation tolerant yeast cells were in G1 phase and had condensed chromosomes. (...)

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