Research, Research Articles

Extracellular DNA secreted in yeast cultures is metabolism-specific and inhibits cell proliferation

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 <i>Escherichia coli</i> cell heterogeneity and ampicillin resistance and persistence

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 <i>Saccharomyces cerevisiae</i> with mutated H3 residues

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 B<sub>12</sub> precursor 5,6-dimethylbenzimidazole is a flavin antagonist in <i>Salmonella</i>

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 <i>KTI13</i> (alias <i>DPH8</i>) operates in the initiation step of diphthamide synthesis on elongation factor 2

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

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.

Metallothionein Cup1 attenuates nitrosative stress in the yeast Saccharomyces cerevisiae

Yuki Yoshikawa1,2,#, Ryo Nasuno1,3,#, Naoki Takaya4 and Hiroshi Takagi1,*

Our findings suggest that the yeast metallothionein Cup1 contributes to nitrosative stress tolerance, possibly as a constitutive rather than an inducible defense mechanism.

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.

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

November 27, 2017

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

November 22, 2017

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

November 20, 2017

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

November 9, 2017

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

November 3, 2017

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

October 2, 2017

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.

Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2

October 2, 2017

The authors descibe the role of the Hsp40 chaperone Ydj1 in Candida albicans, noting its localization to the cytosol and mitochondrial membrane, its necessity for stress responses and filamentation, and its involvement in a protein interaction network related to co-chaperones, filamentation regulators, and mitochondrial processing peptidases, with a particular focus on the impact of Ydj1 on mitochondrial morphology, function, and the import of precursor proteins.

Farnesol inhibits translation to limit growth and filamentation in C. albicans and S. cerevisiae

September 4, 2017

Farnesol, a quorum-sensing molecule, inhibits the switch from yeast to filamentous growth in Candida albicans by impeding translation initiation, differing from fusel alcohols that affect the initiation factor eIF2B, as it disrupts mRNA interaction with the ribosome and prevents preinitiation complex formation.

Cristae architecture is determined by an interplay of the MICOS complex and the F1FO ATP synthase via Mic27 and Mic10

July 20, 2017

This article investigates the roles of MICOS subunits Mic27 and Mic10, revealing their antagonistic and cooperative interactions in crista junction formation and cristae membrane curvature, and proposes a model where F1FO-ATP synthase is connected to MICOS, influencing CJ formation.

Integrative modules for efficient genome engineering in yeast

June 5, 2017

The study introduces a set of vectors with integrative modules designed for effective genome integration into standard marker loci of Saccharomyces cerevisiae, enabling precise expression levels using various promoters and demonstrating the capability of stable multi-gene integration, which is useful for tasks like multi-color cellular imaging and metabolic engineering.

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