Research, Research Articles
Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation
Elisabetta de Alteriis1, Guido Incerti2, Fabrizio Cartenì3, Maria Luisa Chiusano3, Chiara Colantuono3, Emanuela Palomba4, Pasquale Termolino4, Francesco Monticolo3,5, Alfonso Esposito3, Giuliano Bonanomi3,6, Rosanna Capparelli3, Marco Iannaccone3,7, Alessandro Foscari2, Carmine Landi8, Palma Parascandola8, Massimo Sanchez9, Valentina Tirelli9, Bruna de Falco3, Virginia Lanzotti3 and Stefano Mazzoleni3,6
Our study demonstrates that extracellular DNA released by living cells can impact the growth rate of Saccharomyces cerevisiae cultures, showing similarities to extrachromosomal circular DNA and leading to cell cycle arrest in the S phase, suggesting potential new functional roles of exDNA.
Basal level of ppGpp coordinates Escherichia coli cell heterogeneity and ampicillin resistance and persistence
Paulina Katarzyna Grucela1 and Yong Everett Zhang1
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
Nitu Saha1, Swati Swagatika1 and Raghuvir Singh Tomar1
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
Lahiru Malalasekara1 and Jorge C. Escalante-Semerena1,*
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.
Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2
Meike Arend1, Koray Ütkür1, Harmen Hawer1, Klaus Mayer2, Namit Ranjan3, Lorenz Adrian4, Ulrich Brinkmann2 and Raffael Schaffrath1
We show here that apart from its effector role for Elongator-dependent tRNA modification in yeast, Kti13 alias Dph8 also operates in step one of the diphthamide modification pathway.
Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates
Steve Brunette1,#, Anupam Sharma1,2,#, Ryan Bell1, Lawrence Puente1 and Lynn A Megeney1,2,3,*
Caspase 3 activation is a hallmark of cell death and there is a strong correlation between elevated protease activity and evolving pathology in neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS). These results suggest that caspase 3 is not inherently pathogenic, but may act as a compensatory proteostasis factor, to limit TDP-43 protein inclusions and protect organelle function in aggregation related degenerative disease.
GFP fusions of Sec-routed extracellular proteins in Staphylococcus aureus reveal surface-associated coagulase in biofilms
Dominique C. S. Evans1,2,#, Amanda B. Khamas1,#, Lisbeth Marcussen1, Kristian S. Rasmussen3, Janne K. Klitgaard3, Birgitte H. Kallipolitis3, Janni Nielsen1, Daniel E. Otzen1, Mark C. Leake2,4 and Rikke L. Meyer1,5
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.
Atg1, a key regulator of autophagy, functions to promote MAPK activation and cell death upon calcium overload in fission yeast
Teruaki Takasaki1, Ryosuke Utsumi1, Erika Shimada1, Asuka Bamba1, Kanako Hagihara2, Ryosuke Satoh1, and Reiko Sugiura1
Here, we provide evidence that the fission yeast Atg1 regulates cell death responses upon intracellular calcium load in addition to its role in promoting Pmk1 MAPK.
A humanized yeast-based toolkit for monitoring phosphatidylinositol 3-kinase activity at both single cell and population levels
November 12, 2018
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
October 31, 2018
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
October 29, 2018
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
October 16, 2018
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
October 1, 2018
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.
Single telomere length analysis in Ustilago maydis, a high-resolution tool for examining fungal telomere length distribution and C-strand 5’-end processing
August 7, 2018
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
August 1, 2018
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
June 25, 2018
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.
Importance of polyphosphate in the Leishmania life cycle
June 22, 2018
This article explores the importance of polyphosphate (polyP) in Leishmania parasites, emphasizing the role of the polyP polymerase VTC4 and its impact on parasite survival at higher temperatures. Additionally, it discusses the effects of VTC4 knockout in mouse infections, noting a delay in lesion formation and strong pathology in L. major VTC4 knockout, without confirmation through complementation and no alteration in L. guyanensis infections in mice with VTC4 knockdown.
Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence
March 26, 2018
This article describes the effects of salicylate, the main metabolite of aspirin, on S. cerevisiae cells. It outlines how salicylate influences glucose transport, sugar phosphate biosynthesis, and apoptosis, particularly in MnSOD-deficient cells. Furthermore, it emphasizes the significant impact of salicylate on the exit from a quiescent state, inhibiting growth recovery and viability in long-term stationary phase cells. The passage also discusses the potential therapeutic implications of understanding the antagonistic relationship between cAMP and salicylate in targeting quiescent cancer cells with stem-like properties.