Vol. 05, 2018

Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae

Paola Coccetti1,2, Raffaele Nicastro1,3 and Farida Tripodi1,2

This review consolidates current knowledge on the conventional and non-conventional functions of the effector kinase Snf1 in yeast, shedding light on its diverse roles in cellular physiology and energy homeostasis.

An unexpected benefit from E. coli: how enterobactin benefits host health

Aileen K. Sewell1,2, Min Han1,2 and Bin Qi1,2

In this article, the authors comment on the study "Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase" by Qi et al. (Cell, 2018) that uncovered a surprising role for the Escherichia coli-produced siderophore enterobactin (Ent) in facilitating iron uptake by the host, marking a major shift in the understanding of its function and indicating potential new benefits from commensal bacteria in aiding the host's iron homeostasis.

Protective roles of ginseng against bacterial infection

Ye-Ram Kim1 and Chul-Su Yang1

This review highlights the antibacterial effects of ginseng against pathogenic bacterial infections, discussing its regulation of pathogenic factors and proposing the therapeutic potential of ginseng as a natural antibacterial drug to address antibiotic resistance and toxicity in the context of global public health challenges.

A Cinderella story: how the vacuolar proteases Pep4 and Prb1 do more than cleaning up the cell’s mass degradation processes

Winnie Kerstens1,2 and Patrick Van Dijck1,2

This review summarizes the expanded roles of the Saccharomyces cerevisiae vacuolar proteases Pep4 and Prb1 in non-vacuolar activities outside of autophagy, such as programmed cell death, protection from harmful protein forms, and gene expression regulation. The potential implications of these findings for fungal biology and drug target discovery, including insights for mammalian cell studies, are highlighted, emphasizing the need for a deeper understanding of these molecular processes.

The biosynthesis of pyoverdines

Michael T. Ringel1 and Thomas Brüser1

This review provides an overview of pyoverdine biosynthesis, emphasizing the distinctive fluorophore shared by various pyoverdines derived from ferribactins and the role of periplasmic processes in the maturation and modification of these siderophores, critical for the growth and colonization of hosts by fluorescent pseudomonads.

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.

Toxin release mediated by the novel autolysin Cwp19 in Clostridium difficile

Imane El Meouche1 and Johann Peltier2,3

In this article, the authors comment on the study "Cwp19 is a novel lytic transglycosylase involved in stationary-phase autolysis resulting in toxin release in Clostridium difficile" by Wydau-Dematteis (MBio, 2018) that characterizes a novel peptidoglycan hydrolase, Cwp19, in Clostridioides difficile, highlighting its glucose-dependent mediation of toxins secretion and suggesting a potential role in the pathogenesis of this bacterium, contributing to the understanding of these enzymes in C. difficile and their implication in pathogenicity.

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.

Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts

Wei-Dong Zhao1, Dong-Xin Liu1, Yu-Hua Chen1

In this article, the authors comment on the study "Caspr1 is a host receptor for meningitis-causing Escherichia coli" by Zhao et al. (Nat Commun, 2ß18) that identified Caspr1 as a key host receptor for E. coli virulence factor IbeA, facilitating E. coli penetration through the blood-brain barrier (BBB). The research demonstrated that targeting the interaction between IbeA and Caspr1 could potentially neutralize E. coli virulence and prevented meningitis, shedding light on the mechanisms of bacterial invasion into brain endothelial cells and hippocampal neurons.

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Retroviral integration site selection: a running Gag?

Paul Lesbats1,2,3 and Vincent Parissi1,2,3

In this article, the authors comment on the study "Structural basis for spumavirus GAG tethering to chromatin" by Lesbats et al. (Proc Natl Acad Sci, 2018) that revealed that the Gag protein of the spumaretrovirus prototype foamy virus (PFV) directly interacts with the nucleosome acidic patch, acting as a chromatin tether, and its disruption leads to delocalization of viral particles and integration sites, shedding light on the importance of retroviral structural proteins in the selection of integration sites.

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.

Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis

Teresa R. O’Meara1 and Leah E. Cowen1

In this article, the authors comment on the study "High-Throughput Screening Identifies Genes Required for Candida albicans Induction of Macrophage Pyroptosis" by O’Meara et al. (MBio, 2018) that provides a comprehensive analysis of the genetic circuitry in both Candida albicans and host macrophages that leads to pyroptosis, revealing the impact of altered pyroptosis on infection, the role of pyroptosis in facilitating neutrophil accumulation at the site of C. albicans infection, and the decoupling of inflammasome priming and activation in the response to C. albicans infection, thus shedding new light on the factors governing the outcomes of this interaction.

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.

A comparative approach to decipher intestinal animal-microbe associations

Keisuke Nakashima1

In this article, the authors comment on the study "Chitin-based barrier immunity and its loss predated mucus-colonization by indigenous gut microbiota" by Nakashima et al. (Nat Commun, 2018) that used comparative analyses of chordates to investigate the development of animal-microbe associations, suggesting that microbial colonization of the mucus layer over mammalian gastrointestinal epithelium was established upon the loss of ancestral chitin-based barrier immunity, providing insights into the establishment of these associations in an evolutionary context.

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.

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Retroviral integration site selection: a running Gag?

Paul Lesbats1,2,3 and Vincent Parissi1,2,3

In this article, the authors comment on the study "Structural basis for spumavirus GAG tethering to chromatin" by Lesbats et al. (Proc Natl Acad Sci, 2018) that revealed that the Gag protein of the spumaretrovirus prototype foamy virus (PFV) directly interacts with the nucleosome acidic patch, acting as a chromatin tether, and its disruption leads to delocalization of viral particles and integration sites, shedding light on the importance of retroviral structural proteins in the selection of integration sites.

Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis

Teresa R. O’Meara1 and Leah E. Cowen1

In this article, the authors comment on the study "High-Throughput Screening Identifies Genes Required for Candida albicans Induction of Macrophage Pyroptosis" by O’Meara et al. (MBio, 2018) that provides a comprehensive analysis of the genetic circuitry in both Candida albicans and host macrophages that leads to pyroptosis, revealing the impact of altered pyroptosis on infection, the role of pyroptosis in facilitating neutrophil accumulation at the site of C. albicans infection, and the decoupling of inflammasome priming and activation in the response to C. albicans infection, thus shedding new light on the factors governing the outcomes of this interaction.

A comparative approach to decipher intestinal animal-microbe associations

Keisuke Nakashima1

In this article, the authors comment on the study "Chitin-based barrier immunity and its loss predated mucus-colonization by indigenous gut microbiota" by Nakashima et al. (Nat Commun, 2018) that used comparative analyses of chordates to investigate the development of animal-microbe associations, suggesting that microbial colonization of the mucus layer over mammalian gastrointestinal epithelium was established upon the loss of ancestral chitin-based barrier immunity, providing insights into the establishment of these associations in an evolutionary context.

Pathways of host cell exit by intracellular pathogens

Antje Flieger1,#, Freddy Frischknecht2, Georg Häcker3, Mathias W. Hornef4, Gabriele Pradel5

This review provides an overview of the diverse host cell exit strategies employed by intracellular-living bacterial, fungal, and protozoan pathogens, highlighting the commonalities and system-specific variations of these strategies, and discussing potential microbial molecules involved in host cell exit as targets for future intervention approaches.

Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae

Paola Coccetti1,2, Raffaele Nicastro1,3 and Farida Tripodi1,2

This review consolidates current knowledge on the conventional and non-conventional functions of the effector kinase Snf1 in yeast, shedding light on its diverse roles in cellular physiology and energy homeostasis.

An unexpected benefit from E. coli: how enterobactin benefits host health

Aileen K. Sewell1,2, Min Han1,2 and Bin Qi1,2

In this article, the authors comment on the study "Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase" by Qi et al. (Cell, 2018) that uncovered a surprising role for the Escherichia coli-produced siderophore enterobactin (Ent) in facilitating iron uptake by the host, marking a major shift in the understanding of its function and indicating potential new benefits from commensal bacteria in aiding the host's iron homeostasis.

Protective roles of ginseng against bacterial infection

Ye-Ram Kim1 and Chul-Su Yang1

This review highlights the antibacterial effects of ginseng against pathogenic bacterial infections, discussing its regulation of pathogenic factors and proposing the therapeutic potential of ginseng as a natural antibacterial drug to address antibiotic resistance and toxicity in the context of global public health challenges.

A Cinderella story: how the vacuolar proteases Pep4 and Prb1 do more than cleaning up the cell’s mass degradation processes

Winnie Kerstens1,2 and Patrick Van Dijck1,2

This review summarizes the expanded roles of the Saccharomyces cerevisiae vacuolar proteases Pep4 and Prb1 in non-vacuolar activities outside of autophagy, such as programmed cell death, protection from harmful protein forms, and gene expression regulation. The potential implications of these findings for fungal biology and drug target discovery, including insights for mammalian cell studies, are highlighted, emphasizing the need for a deeper understanding of these molecular processes.

The biosynthesis of pyoverdines

Michael T. Ringel1 and Thomas Brüser1

This review provides an overview of pyoverdine biosynthesis, emphasizing the distinctive fluorophore shared by various pyoverdines derived from ferribactins and the role of periplasmic processes in the maturation and modification of these siderophores, critical for the growth and colonization of hosts by fluorescent pseudomonads.

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Microbial wars: competition in ecological niches and within the microbiome

Maria A. Bauer1, Katharina Kainz1, Didac Carmona-Gutierrez1 and Frank Madeo1,2

In this Editorial Bauer et al. provide a brief overview on microbial competition and discuss some of its roles and consequences that directly affect humans.

Exploring the mechanism of amebic trogocytosis: the role of amebic lysosomes

Allissia A. Gilmartin1 and William A. Petri, Jr1,2,3

In this article, the authors comment on the study "Inhibition of Amebic Lysosomal Acidification Blocks Amebic Trogocytosis and Cell Killing" by Gilmartin et al. (MBio, 2017), discussing the the role of amebic lysosomes in Trogocytosis, the intracellular transfer of fragments of cell material.

Evolution of substrate specificity in the Nucleobase-Ascorbate Transporter (NAT) protein family

March 22, 2018

L-ascorbic acid (vitamin C) is an essential metabolite in animals and plants due to its role as an enzyme co-factor and antioxidant activity. Here, Kourkoulou et al. show further evidence that ascorbate-specific Nucleobase-Ascorbate Transporters (NATs) evolved by optimization of a sub-function of ancestral nucleobase transporters.

Helicobacter hepaticus polysaccharide induces an anti-inflammatory response in intestinal macrophages

March 22, 2018

In this article, the authors comment on the study "A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages. " by Danne et al, (Cell Host Microbe 2017), discussing the interactions between H. hepaticus and intestinal macrophages that promote mutualism.

Endolysosomal pathway activity protects cells from neurotoxic TDP-43

March 21, 2018

In this article, the authors comment on the study "TDP-43 controls lysosomal pathways thereby determining its own clearance and cytotoxicity" by Leibiger et al. (Hum Mol Genet, 2018), proposing that ameliorating endolysosomal pathway activity enhances cell survival in TDP‑43-associated diseases.

Valine biosynthesis in Saccharomyces cerevisiae is regulated by the mitochondrial branched-chain amino acid aminotransferase Bat1

March 21, 2018

In Saccharomyces cerevisiae, the yeast, the Bat1 and Bat2 proteins, which are branched-chain amino acid aminotransferases, play distinct roles in valine biosynthesis and cell growth regulation, with Bat1 primarily located in the mitochondria and Bat2 in the cytosol, and the mitochondria being identified as the major site of valine biosynthesis in this yeast.

Microbial competition between Escherichia coli and Candida albicans reveals a soluble fungicidal factor

March 7, 2018

Localized and systemic fungal infections caused by Candida albicans can lead to significant mortality and morbidity. Here, Cabral et al. show that E. coli produces a soluble factor that kills C. albicans in a magnesium-dependent fashion such that depletion of available magnesium is essential for toxicity.

Spontaneous mutations in CYC8 and MIG1 suppress the short chronological lifespan of budding yeast lacking SNF1/AMPK

February 19, 2018

Chronologically aging yeast cells are prone to adaptive regrowth, whereby mutants with a survival advantage spontaneously appear and re-enter the cell cycle in stationary phase cultures. Here, Magani et al. identified specific downstream SNF1 targets responsible for CLS extension during CR.

Decreasing cytosolic translation is beneficial to yeast and human Tafazzin-deficient cells

February 18, 2018

Cardiolipin (CL) optimizes diverse mitochondrial processes, including oxidative phosphorylation (OXPHOS). Here, de Taffin de Tilques et al. describe that a diminished capacity of CL remodeling deficient cells to preserve protein homeostasis is likely an important factor contributing to the pathogenesis of Barth Syndrome (BTHS) and identifies cytosolic translation as a potential therapeutic target for the treatment of this disease.

Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles

February 18, 2018

In this article, the authors comment on the study "A Specialized Peptidoglycan Synthase Promotes Salmonella Cell Division inside Host Cells" by Castanheira et al. (mBio, 2017), discussing insights in two distinct penicillin binding proteins that promote cell division in different Salmonella lifestyles.

Production of poly-β-1,6-N-acetylglucosamine by MatAB is required for hyphal aggregation and hydrophilic surface adhesion by Streptomyces

February 12, 2018

In this article van Dissel et al. describe new insights to allow better control of liquid-culture morphology of streptomycetes, which may be harnessed to improve growth and industrial exploitation of these highly versatile natural product and enzyme producers.

Impact of F1Fo-ATP-synthase dimer assembly factors on mitochondrial function and organismic aging

January 30, 2018

In aerobic organisms, mitochondrial F1Fo-ATP-synthase is the major site of ATP production. Here, Rampello et al. report on the role of the two dimer assembly factors PaATPE and PaATPG of the aging model Podospora anserina validating a model that links mitochondrial membrane remodeling to aging and identify specific molecular components triggering this process.