Research, Research Articles
A humanized yeast-based toolkit for monitoring phosphatidylinositol 3-kinase activity at both single cell and population levels
Julia María Coronas-Serna1, Teresa Fernández-Acero1, María Molina1 and Víctor J. Cid1
In this study, a humanized yeast system for functional studies on higher eukaryotic Phosphatidylinositol 3-kinase (PI3K) was developed by restricting PI3K activity in yeast to specific plasma membrane microdomains, utilizing engineered reporters to monitor activity at a single-cell level and employing novel tools to study the performance of yeast plasma membrane (PM) microdomain-directed PI3K, revealing location-specific effects on yeast growth and endocytosis.
A chemical genetic screen reveals a role for proteostasis in capsule and biofilm formation by Cryptococcus neoformans
François L. Mayer1, Eddy Sánchez-León1, James W. Kronstad1
This study demonstrates that the bipolar disorder drug lithium inhibits the formation of key virulence factors, biofilm, and polysaccharide capsule, in Cryptococcus neoformans by dysregulating the ubiquitin/proteasome system, shedding light on the impact of lithium and providing insights into potential alternative pharmaceutical approaches for combating this fungal pathogen.
Nutritional and meiotic induction of transiently heritable stress resistant states in budding yeast
Heldder Gutierrez1, Bakhtiyar Taghizada1, and Marc D. Meneghini1
This study demonstrates that transient exposures to environmental stresses induce persistent states of elevated stress resistance in yeast cells, termed cellular memory, suggesting a form of epigenetic inheritance, and shows that this phenomenon occurs not only in meiotically produced spores but also in haploid cells subjected to glucose withdrawal, adding new insights into the developmentally and nutritionally induced cellular memory.
Specific mutations in the permease domain of septal protein SepJ differentially affect functions related to multicellularity in the filamentous cyanobacterium Anabaena
Félix Ramos-León1, Sergio Arévalo1, Vicente Mariscal1 and Enrique Flores1
In this study, the multifunctional roles of the SepJ protein in the multicellular function of the Anabaena filament were investigated, revealing that specific amino acids and stretches within the protein are essential for the formation of long filaments, heterocyst differentiation, and intercellular communication, shedding light on the structure and diverse functions of SepJ in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.
Trehalose-6-phosphate promotes fermentation and glucose repression in Saccharomyces cerevisiae
Rebeca L. Vicente1,2, Lucie Spina1, Jose P.L. Gómez1, Sebastien Dejean3, Jean-Luc Parrou1 and Jean Marie François1,4
This study examined the capability of trehalose-6-phosphate synthase (TPS1) homologues from various species to complement the phenotypic defects of a Saccharomyces cerevisiae tps1 mutant, resulting in the classification of complementation into different groups based on metabolic patterns and fermentation capacity, shedding light on the role of TPS1 and trehalose-6-phosphate (T6P) as critical factors in sugar fermentation and glucose repression.
The translationally controlled tumor protein TCTP is involved in cell cycle progression and heat stress response in the bloodstream form of Trypanosoma brucei
Borka Jojic1, Simona Amodeo1,2 and Torsten Ochsenreiter1
This study reveals the involvement of the translationally controlled tumor protein TCTP in cell cycle regulation and heat stress response in the bloodstream form of Trypanosoma brucei, shedding light on its role in these cellular processes.
Single telomere length analysis in Ustilago maydis, a high-resolution tool for examining fungal telomere length distribution and C-strand 5’-end processing
Ganduri Swapna1, Eun Young Yu1 and Neal F. Lue1, 2
This article introduces the development of single telomere length analysis (STELA) for Ustilago maydis, a basidiomycete fungus, enabling the precise measurement of telomere lengths and distributions. The study demonstrates STELA's utility in revealing the existence of relatively short telomeres in wild-type cells, preferential loss of long telomeres in a mutant defective in telomere replication, and the characterization of telomere C-strand 5’ ends, highlighting U. maydis as a strong model for telomere research.
Temporal analysis of the autophagic and apoptotic phenotypes in Leishmania parasites
Louise Basmaciyan1, Laurence Berry2, Julie Gros3, Nadine Azas3 and Magali Casanova3
This article details a comprehensive analysis of miltefosine-induced cell death and autophagy in Leishmania major, providing criteria for clear identification of apoptotic and autophagic cells, demonstrating the sequential nature of autophagy followed by apoptosis in nutrient-deprived conditions, and cautioning against using the generic kinase inhibitor staurosporine as a Leishmania apoptosis inducer, with the aim of improving the understanding of these processes and their targeting for new anti-leishmanial drugs.
Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress
Stephen D. Willis1, David C. Stieg1, Kai Li Ong2, Ravina Shah1,3, Alexandra K. Strich1,4, Julianne H. Grose2 and Katrina F. Cooper1
This article explores the response of eukaryotic cells to environmental stress, highlighting the role of the conserved cyclin C-Cdk8 kinase in determining pro-survival or pro-death programs. Specifically, it discusses how oxidative stress triggers the destruction of Med13 by the SCFGrr1 ubiquitin ligase, releasing cyclin C to promote mitochondrial fission and cell death in Saccharomyces cerevisiae. Additionally, it reveals that the AMP kinase Snf1 activates a separate degron in Med13, contributing to the complex regulation of Med13 degradation following H2O2 stress through the coordination of the cell wall integrity and MAPK pathways.
Basal level of ppGpp coordinates Escherichia coli cell heterogeneity and ampicillin resistance and persistence
October 25, 2023
The universal stringent response alarmone ppGpp (guanosine penta and tetra phosphates) plays a crucial role in various aspects of fundamental cell physiology (e.g., cell growth rate, cell size) and thus bacterial tolerance to and survival of external stresses, including antibiotics. In tihs study, we discuss the fundamental role of basal level of ppGpp in regulating cell homogeneity and ampicillin persistence.
Investigation of the acetic acid stress response in Saccharomyces cerevisiae with mutated H3 residues
August 18, 2023
Yeast cells respond to acetic acid in diverse ways. Here, we have elucidated the deleterious effects of acetic acid on different histone mutants
The coenzyme B12 precursor 5,6-dimethylbenzimidazole is a flavin antagonist in Salmonella
August 17, 2023
Here we investigated why 5,6-dimethylbenzimidazole (DMB) inhibits in S. Typhimurium. Briefly, we determined that the structural similarities of the substituted benzene ring of DMB with the isoalloxazine moiety of flavins is responsible for the deleterious effects of this CoB12 precursor.
GFP fusions of Sec-routed extracellular proteins in Staphylococcus aureus reveal surface-associated coagulase in biofilms
June 28, 2023
We show that msfGFP can be used to generate extracellular fluorescent fusion proteins in S. aureus, applicable for proteins that are secreted through the Sec pathway. When fused to coagulase, msfGFP did not hinder the biological function, and the fusion protein localised to the fibrin pseudocapsule surrounding clusters of S. aureus cells.
TL-532, a novel specific Toll-like receptor 3 agonist rationally designed for targeting cancers: discovery process and biological characterization
April 19, 2023
In the present study, we identified a new family of TLR3 agonists that activates myeloid cells, triggers the secretion of pro-inflammatory cytokines in both myeloid and cancer cells, and induces apoptosis specifically in cancer cells.
Acetate modulates the inhibitory effect of Lactobacillus gasseri against the pathogenic yeasts Candida albicans and Candida glabrata
March 21, 2023
The results herein described advance the design of new anti-Candida therapies based on probiotics, in particular, those based on vaginal lactobacilli species, helping to reduce the significant burden that infections caused by Candida have today in human health.
D-Serine reduces the expression of the cytopathic genotoxin colibactin
March 8, 2023
Sensing and responding to environmental cues and signalling molecules is crucial for bacterial survival. In this study we have identified a D-amino acid that has a strong regulatory effect on the pks genomic island which encodes for biosynthesis genes for the genotoxic compound colibactin.
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 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.