The p53 DNA-Binding (Core) Domain can form a prion that seeds prion formation in full-length p53
In yeast the p53 core-domain forms a self-propagating prion that inactivates a reporter and converts untagged full-length p53 to a prion. R175H in the tagged chimera shows 18x higher prionization, linking it to p53 inactivation in human cancers.
Sorbic acid triggers rapid formation of proteasome storage granules in Saccharomyces cerevisiae
This study demonstrates that sorbic acid, a common food preservative, induces the fastest reported proteasome storage granule (PSG) formation in yeast within 30 min, highlighting differences from other PSG-inducing conditions like acetic acid stress.
A time-resolved high-throughput screening of fission yeast deletion mutants for oxidative stress resistance
By capturing dynamic trajectories rather than static outcomes, this study exposes hidden layers of growth under oxidative stress and identifies new genetic determinants of cellular resilience in fission yeast.
Clonal spread and environmental persistence of carbapenem-resistant high-risk Pseudomonas aeruginosa in critical-care units of a Chilean national referral center for burn and trauma patients (2022)
This study highlight the circulation of high-risk P. aeruginosa clones in Chile and underscore the importance of molecular epidemiology in guiding infection control, optimizing antimicrobial therapy, and mitigating the clinical and economic burden of CRPA.
The p53 DNA-Binding (Core) Domain can form a prion that seeds prion formation in full-length p53
Kadouch et al.In yeast the p53 core-domain forms a self-propagating prion that inactivates a reporter and converts untagged full-length p53 to a prion. R175H in the tagged chimera shows 18x higher prionization, linking it to p53 inactivation in human cancers.
Sorbic acid triggers rapid formation of proteasome storage granules in Saccharomyces cerevisiae
Tanaka et al.This study demonstrates that sorbic acid, a common food preservative, induces the fastest reported proteasome storage granule (PSG) formation in yeast within 30 min, highlighting differences from other PSG-inducing conditions like acetic acid stress.
A time-resolved high-throughput screening of fission yeast deletion mutants for oxidative stress resistance
Pirsalehi et al.By capturing dynamic trajectories rather than static outcomes, this study exposes hidden layers of growth under oxidative stress and identifies new genetic determinants of cellular resilience in fission yeast.
Clonal spread and environmental persistence of carbapenem-resistant high-risk Pseudomonas aeruginosa in critical-care units of a Chilean national referral center for burn and trauma patients (2022)
Ibarra et al.This study highlight the circulation of high-risk P. aeruginosa clones in Chile and underscore the importance of molecular epidemiology in guiding infection control, optimizing antimicrobial therapy, and mitigating the clinical and economic burden of CRPA.
The transcriptome of dendritic cells redraws the boundaries between pathogenicity and commensalism in yeast
Rizzetto et al.Our immune system meets many fungi, but reacts strongly to only a few. The comparison of key fungal species showed that responses differ mainly in timing and not just genes, highlighting the need to rethink what makes fungi harmful vs. harmless.
Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in Saccharomyces cerevisiae
Olgun et al.This study demonstrates that the conserved yeast protein Moh1 links metabolism, gene expression, and cell structure, thereby altering cell envelope permeability and leading to selective stress responses.
Fungistatic effect of sorbic acid on yeast cells via translational repression involving eIF2α phosphorylation and formation of Ded1- and eIF2B-granules
Yoshiyama et al.The findings of this study provide new insights into the physiological effects of sorbic acid on yeast cells, specifically regarding the regulation of translation-related factors.
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
Michael E. Bond et al.Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.
Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae
Markus M.M. Bisschops et al.Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of…
DNA damage checkpoint adaptation genes are required for division of cells harbouring eroded telomeres
Sofiane Y. Mersaoui et al.In budding yeast, telomerase and the Cdc13p protein are two key players acting to ensure telomere stability. This article shows that while the capping process can be flexible, it takes a very specific genetic setup to allow a change from canonical capping to alternative capping.
The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway
Chunyan Jin et al.Oxidative stress stimulates the Rho1 GTPase, which in turn induces the cell wall integrity (CWI) MAP kinase cascade. CWI activation promotes stress-responsive gene expression through activation of transcription factors (Rlm1, SBF) and nuclear release and subsequent destruction of the repressor cyclin C. This study reports that, in response to high hydrogen peroxide exposure, or in the presence of constitutively active Rho1, cyclin C still translocates to the cytoplasm and is degraded in cells lacking Bck1, the MAPKKK of the CWI pathway.
Formyl-methionine as a degradation signal at the N-termini of bacterial proteins
Konstantin I. Piatkov et al.Varshavsky and colleagues solve a long-standing mystery in proteolysis! In bacteria, all nascent proteins bear the pretranslationally formed N-terminal formyl-methionine (fMet) residue. The fMet residue is cotranslationally deformylated by a ribosome-associated deformylase. The formylation of N-terminal Met in bacterial proteins is not strictly essential for either translation or cell viability. Moreover, protein synthesis by the cytosolic ribosomes of eukaryotes does not involve the formylation of N-terminal Met. What, then, is the main biological function of this metabolically costly, transient, and not strictly essential modification of N‑terminal Met, and why has Met formylation not been eliminated during bacterial evolution? One possibility is that the similarity of the formyl and acetyl groups, their identical locations in…
A single mutation in the 15S rRNA gene confers non sense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria
Ali Gargouri et al.This article presents the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. A hypothetical mechanism of suppression by “ribosome shifting” is also discussed in view of the nature of mutations suppressed and not suppressed.
The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei
Hazel Xinyu Koh et al.Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization. We measured drug concentrations that inhibit cell proliferation by 50% (IC50) for several compounds, chosen based on their lysosomotropic effects previously reported in Plasmodium falciparum. The lysosomal effects and cell death induced by L-leucyl-L-leucyl methyl ester (LeuLeu-OMe) were further analyzed by flow cytometry and immunofluorescence analyses of different lysosomal markers…
In Entamoeba histolytica, a BspA family protein is required for chemotaxis toward tumour necrosis factor
Anne Silvestre et al.Background: Entamoeba histolytica cell migration is essential for the development of human amoebiasis (an infectious disease characterized by tissue invasion and destruction). The tissue inflammation associated with tumour necrosis factor (TNF) secretion by host cells is a well-documented feature of amoebiasis. Tumour necrosis factor is a chemoattractant for E. histolytica, and the parasite may have a TNF receptor at its cell surface. Methods: confocal microscopy, RNA Sequencing, bioinformatics, RNA antisense techniques and histological analysis of human colon explants were used to characterize the interplay between TNF and E. histolytica. Results: an antibody against human TNF receptor 1 (TNFR1) stained the E. histolytica trophozoite…
Biofilm tolerance, resistance and infections increasing threat of public health
Yang et al.The review explores the role of biofilms in the development of bacterial resistance mechanisms and proposed therapeutic intervention strategies for biofilm related diseases.
Infinity war: Trichomonas vaginalis and interactions with host immune response
Bongiorni Galego and TascaTrichomonas vaginalis is the pathological agent of human trichomoniasis with an incidence of 156 million cases worldwide. This review highlights parasite strategies to activate and stimulate or evade variated and complex immunological mechanisms related to the symptoms and clinical complications observed here.
Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy
Terrisse et al.Prostate cancer (PC) can be kept in check by androgen deprivation therapy (ADT, usually with the androgen synthesis inhibitor abiraterone acetate or the androgen receptor antagonist such as enzalutamide) until the tumor evolves to castration-resistant prostate cancer (CRPC). The transition of hormone-sensitive PC (HSPC) to CPRC has been explained by cancer cell-intrinsic resistance mechanisms. Recent data indicate that this transition is also marked by cancer cell-extrinsic mechanisms such as the failure of ADT-induced PC immunosurveillance, which depends on the presence of immunostimulatory bacteria in the gut. Moreover, intestinal bacteria that degrade drugs used for ADT, as well as bacteria that produce androgens, can interfere with the efficacy of ADT. Thus, specific bacteria in the gut serve as a source of testosterone, which accelerates prostate cancer progression, and men with CRPC exhibit an increased abundance of such bacteria with androgenic functions. In conclusion, the response of PC to ADT is profoundly influenced by the composition of the microbiota with its immunostimulatory, immunosuppressive and directly ADT-subversive elements.
Occurrence and potential mechanism of holin-mediated non-lytic protein translocation in bacteria
Brüser and Mehner-BreitfeldHolins are generally believed to generate large membrane lesions that permit the passage of endolysins across the cytoplasmic membrane of prokaryotes, ultimately resulting in cell wall degradation and cell lysis. However, there are more and more examples known for non-lytic holin-dependent secretion of proteins by bacteria, indicating that holins somehow can transport proteins without causing large membrane lesions. Phage-derived holins can be used for a non-lytic endolysin translocation to permeabilize the cell wall for the passage of secreted proteins. In addition, clostridia, which do not possess the Tat pathway for transport of folded proteins, most likely employ non-lytic holin-mediated transport also for secretion of toxins and bacteriocins that are incompatible with the general Sec pathway. The mechanism for non-lytic holin-mediated transport is (…)
Swimming faster despite obstacles: a universal mechanism behind bacterial speed enhancement in complex fluids
Kamdar and Cheng.Bacteria constitute about 15% of global biomass and their natural environments often contain polymers and colloids, which show complex flow properties. It is crucial to study their motion in such environments to understand their growth and spreading as well as to design synthetic microswimmers for biomedical applications. Bacterial motion in complex viscous environments, although extensively studied over the past six decades, still remains poorly understood. In our recent study combining experimental data and theoretical analysis, we found a surprising similarity between bacterial motion in dilute colloidal suspensions and polymer solutions, which challenged the established view on the role of polymer dynamics on bacterial speed enhancement. We subsequently developed a physical model that provides a universal mechanism explaining bacterial speed enhancement (…)
A roadmap for designing narrow-spectrum antibiotics targeting bacterial pathogens
Cao et al.This comment discusses the article “Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile” by Cao et al. (2022, Nature).
Breaking the clip for cargo unloading from motor proteins: mechanism and significance
Obara and KamuraThe mitochondrion is an essential organelle involved in ATP generation, lipid metabolism, regulation of calcium ions, etc. Therefore, it should be inherited properly by newly generated cells. In the budding yeast Saccharomyces cerevisiae, mitochondria are passed on to daughter cells by the motor protein, Myo2, on the actin cable. The mitochondria and Myo2 are connected via the adaptor protein Mmr1. After reaching daughter cells, mitochondria are released from the actin-myosin machinery and move dynamically. In our recent paper (Obara K et al. (2022), Nat Commun, doi:10.1038/s41467-022-29704-8), we demonstrated that the regulated proteolysis of Mmr1 is required for the unloading of mitochondria from Myo2 in daughter cells. Sequential post-translational modifications of Mmr1, i.e., phosphorylation followed by ubiquitination, are essential for Mmr1 degradation and mitochondrial release from Myo2. Defects in Mmr1 degradation cause stacking and deformation of mitochondria at the bud-tip and bud-neck, where Myo2 accumulates. Compared to wild-type cells, mutant cells with defects in Mmr1 degradation possess an elevated mitochondrial membrane potential and produce higher levels of reactive oxygen species (ROS), along with hypersensitivity to oxidative stress.
Non-genetic impact factors on chronological lifespan and stress resistance of baker’s yeast
Sauer and MattanovichThis article comments on work published by Bisschops et al. (Microbial Cell, 2015), which illustrates how important the choice of the experimental setup is and how culture conditions influcence cellular aging and survival in biotechnological processes.
What’s old is new again: yeast mutant screens in the era of pooled segregant analysis by genome sequencing
Curtin and CordenteThis article comments on work published by Den Abt et al. (Microbial Cell, 2016), which identified genes involved in ethyl acetate formation in a yeast mutant screen based on a new approach combining repeated rounds of chemical mutagenesis and pooled segregant analysis by whole genome sequencing.
The complexities of bacterial-fungal interactions in the mammalian gastrointestinal tract
Lopez-Medina and KohThis article comments on work published by Lopez-Medina et al. (PLoS Pathog, 2015) and Fan et al. (Nat Med, 2015), which utilize an “artificial” niche, the antibiotic-treated gut with concomitant pathogenic microbe expansion, to gain insight in bacterial-fungal interactions in clinically common scenarios.
Gearing up for survival – HSP-containing granules accumulate in quiescent cells and promote survival
Yu and DangThis article comments on work published by Lee et al. (Microbial Cell, 2016), which reports that distinct granules are formed in quiescent and non-quiescent cells, which determines their respective cell fates.
Yeast screening platform identifies FDA-approved drugs that reduce Aβ oligomerization
Amen and KaganovichThis article comments on work published by Park et al. (Microbial Cell, 2016), which discovered a number of small molecules capable of modulating Aβ aggregation in a yeast model.
Groupthink: chromosomal clustering during transcriptional memory
MoranoIn this article, the authors comment on the study “NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering.” by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.
Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration
Amit Shrestha et al.Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.
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Peer-reviewed, open-access research using unicellular organisms (and multicellular microorganisms) to understand cellular responses and human disease.
The journal (founded in 2014) is led by its Editors-in-Chief Frank Madeo, Didac Carmona-Gutierrez, and Guido Kroemer
Microbial Cell has been publishing original scientific literature since 2014, and from the very beginning has been managed by active scientists through an independent Publishing House (Shared science Publishers). The journal was conceived as a platform to acknowledge the importance of unicellular organisms, both as model systems as well as in the biological context of human health and disease.
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2022: Microbial Cell is listed in the Journal Citation Reports™ (JCR), and obtains its first official Journal Impact Factor™ (JIF) for the year 2021: 5.316.
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Similar environments but diverse fates: Responses of budding yeast to nutrient deprivation.
HonigbergDiploid budding yeast (Saccharomyces cerevisiae) can adopt one of several alternative differentiation fates in response to nutrient limitation, and each of these fates provides distinct biological functions. When different strain backgrounds are taken into account, these various fates occur in response to similar environmental cues, are regulated by the same signal transduction pathways, and share many of the same master regulators. I propose that the relationships between fate choice, environmental cues and signaling pathways are not Boolean, but involve graded levels of signals, pathway activation and master-regulator activity.