Vol. 05, 2018

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.

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.

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.

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Molecular signature of the imprintosome complex at the mating-type locus in fission yeast

Célia Raimondi1, Bernd Jagla2, Caroline Proux3, Hervé Waxin4, Serge Gangloff1, Benoit Arcangioli1

Genetic and molecular studies have indicated that an epigenetic imprint at mat1, the sexual locus of fission yeast, initiates mating type switching. Here, Raimondi et al. characterized the recruitment of early players of mating type switching at the mat1 region and suggest a nucleoprotein protective structure defined as imprintosome.

Leishmania guyanensis parasites block the activation of the inflammasome by inhibiting maturation of IL-1β

Mary-Anne Hartley1,¶, Remzi O. Eren1,¶, Matteo Rossi1, Florence Prevel1, Patrik Castiglioni1, Nathalie Isorce1, Chantal Desponds1, Lon-Fye Lye2, Stephen M. Beverley2, Stefan K. Drexler1,&, Nicolas Fasel1,&

The various symptomatic outcomes of cutaneous leishmaniasis relates to the type and potency of its underlying inflammatory responses mediated by Toll-Like-Receptor-3 (TLR3). Here, Hartely et al. investigated other innate pattern recognition receptors capable of reacting to dsRNA and potentially contributing to LRV1-mediated inflammatory pathology. They postulate that avoidance of the inflammasome pathways is likely an important mechanism of virulence in Leishmania infection irrespective of the LRV1-status.

A novel system to monitor mitochondrial translation in yeast

Tamara Suhm1, Lukas Habernig2, Magdalena Rzepka1, Jayasankar Mohanakrishnan Kaimal3, Claes Andréasson3, Sabrina Büttner2,3 and Martin Ott1

In this study Suhm et al. present a novel system to monitor mitochondrial translation by detection of mitochondrial GFP-translation through fluorescence microscopy and flow cytometry in functional mitochondria. This novel tool allows the investigation of the function and regulation of mitochondrial translation during stress signaling, aging and mitochondrial biogenesis.

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

Marie-Anne Deprez1,°, Elja Eskes1,°, Tobias Wilms1, Paula Ludovico2, Joris Winderickx1

In this article, Deprez et al. discuss accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

Guidelines and recommendations on yeast cell death nomenclature

Didac Carmona-Gutierrez1,‡,*, Maria Anna Bauer1,‡, Andreas Zimmermann1, Andrés Aguilera2, Nicanor Austriaco3, Kathryn Ayscough4, Rena Balzan5, Shoshana Bar-Nun6, Antonio Barrientos7,8, Peter Belenky9, Marc Blondel10, Ralf J. Braun11, Michael Breitenbach12, William C. Burhans13, Sabrina Büttner1,14, Duccio Cavalieri15, Michael Chang16, Katrina F. Cooper17, Manuela Côrte-Real18, Vítor Costa19–21, Christophe Cullin22, Ian Dawes23, Jörn Dengjel24, Martin B. Dickman25, Tobias Eisenberg1,26, Birthe Fahrenkrog27, Nicolas Fasel28, Kai-Uwe Fröhlich1, Ali Gargouri29, Sergio Giannattasio30, Paola Goffrini31, Campbell W. Gourlay32, Chris M. Grant33, Michael T. Greenwood34, Nicoletta Guaragnella30, Thomas Heger35, Jürgen Heinisch36, Eva Herker37, Johannes M. Herrmann38, Sebastian Hofer1, Antonio Jiménez-Ruiz39, Helmut Jungwirth1, Katharina Kainz1, Dimitrios P. Kontoyiannis40, Paula Ludovico41,42, Stéphen Manon43, Enzo Martegani44, Cristina Mazzoni45, Lynn A. Megeney46–48, Chris Meisinger49, Jens Nielsen50–52, Thomas Nyström53, Heinz D. Osiewacz54, Tiago F. Outeiro55–58, Hay-Oak Park59, Tobias Pendl1, Dina Petranovic50,51, Stephane Picot60,61, Peter Polčic62, Ted Powers63, Mark Ramsdale64, Mark Rinnerthaler65, Patrick Rockenfeller1,32, Christoph Ruckenstuhl1, Raffael Schaffrath66, Maria Segovia67, Fedor F. Severin68, Amir Sharon69, Stephan J. Sigrist70, Cornelia Sommer-Ruck1, Maria João Sousa18, Johan M. Thevelein71,72, Karin Thevissen73, Vladimir Titorenko74, Michel B. Toledano75, Mick Tuite32, F.-Nora Vögtle49, Benedikt Westermann11, Joris Winderickx76, Silke Wissing77, Stefan Wölfl78, Zhaojie J. Zhang79, Richard Y. Zhao80, Bing Zhou81, Lorenzo Galluzzi82–84,*, Guido Kroemer84–90,*, Frank Madeo1,26,*

In this review, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of yeast.

Burkholderia gladioli strain NGJ1 deploys a prophage tail-like protein for mycophagy

Rahul Kumar1, Sunil Kumar Yadav1, Durga Madhab Swain1 and Gopaljee Jha1

In this article, the authors comment on the study "A prophage tail-like protein is deployed by Burkholderia bacteria to feed on fungi" by Swain et al. (Nature Communications, 2017), discussing that a prophage tail-like protein (Bg_9562) is essential for mycophagy. The protein may help the bacteria to survive in certain ecological niches and, considering its broad-spectrum antifungal activity, may be potentially useful in biotechnological applications to control fungal diseases.

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

Camille Danne1 and Fiona Powrie1

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

Christine Leibiger1,#, Jana Deisel1,#, Andreas Aufschnaiter2, Stefanie Ambros1, Maria Tereshchenko1, Bert M. Verheijen3,4, Sabrina Büttner2,5, and Ralf J. Braun1

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.

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

Sónia Castanheira1, Juan J. Cestero1, Francisco García-del Portillo1, M. Graciela Pucciarelli1,2,3

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.

New perspectives from South-Y-East, not all about death

A report of the 12th lnternational Meeting on Yeast Apoptosis in Bari, Italy, May 14th-18th, 2017

Nicoletta Guaragnella1,#, Mariarita Stirpe2,#, William Burhans3, Manuela Côrte-Real4, Campbell Gourlay5, Paula Ludovico6,7, Frank Madeo8,9, Dina Petranovic10, Joris Winderickx11, Cristina Mazzoni2 and Sergio Giannattasio1

In this article Guaragnella et al. report on the 12th International Meeting on Yeast Apoptosis (IMYA12), which was held in Bari, Italy from May 14th to 18th, 2017, where more than 100 participants, among which senior and young scientists from Europe, USA, North Africa and Japan, had an intense and open exchange of achievements and ideas in the field of yeast regulated cell death (RCD).

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

Marie-Anne Deprez1,°, Elja Eskes1,°, Tobias Wilms1, Paula Ludovico2, Joris Winderickx1

In this article, Deprez et al. discuss accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

Guidelines and recommendations on yeast cell death nomenclature

Didac Carmona-Gutierrez1,‡,*, Maria Anna Bauer1,‡, Andreas Zimmermann1, Andrés Aguilera2, Nicanor Austriaco3, Kathryn Ayscough4, Rena Balzan5, Shoshana Bar-Nun6, Antonio Barrientos7,8, Peter Belenky9, Marc Blondel10, Ralf J. Braun11, Michael Breitenbach12, William C. Burhans13, Sabrina Büttner1,14, Duccio Cavalieri15, Michael Chang16, Katrina F. Cooper17, Manuela Côrte-Real18, Vítor Costa19–21, Christophe Cullin22, Ian Dawes23, Jörn Dengjel24, Martin B. Dickman25, Tobias Eisenberg1,26, Birthe Fahrenkrog27, Nicolas Fasel28, Kai-Uwe Fröhlich1, Ali Gargouri29, Sergio Giannattasio30, Paola Goffrini31, Campbell W. Gourlay32, Chris M. Grant33, Michael T. Greenwood34, Nicoletta Guaragnella30, Thomas Heger35, Jürgen Heinisch36, Eva Herker37, Johannes M. Herrmann38, Sebastian Hofer1, Antonio Jiménez-Ruiz39, Helmut Jungwirth1, Katharina Kainz1, Dimitrios P. Kontoyiannis40, Paula Ludovico41,42, Stéphen Manon43, Enzo Martegani44, Cristina Mazzoni45, Lynn A. Megeney46–48, Chris Meisinger49, Jens Nielsen50–52, Thomas Nyström53, Heinz D. Osiewacz54, Tiago F. Outeiro55–58, Hay-Oak Park59, Tobias Pendl1, Dina Petranovic50,51, Stephane Picot60,61, Peter Polčic62, Ted Powers63, Mark Ramsdale64, Mark Rinnerthaler65, Patrick Rockenfeller1,32, Christoph Ruckenstuhl1, Raffael Schaffrath66, Maria Segovia67, Fedor F. Severin68, Amir Sharon69, Stephan J. Sigrist70, Cornelia Sommer-Ruck1, Maria João Sousa18, Johan M. Thevelein71,72, Karin Thevissen73, Vladimir Titorenko74, Michel B. Toledano75, Mick Tuite32, F.-Nora Vögtle49, Benedikt Westermann11, Joris Winderickx76, Silke Wissing77, Stefan Wölfl78, Zhaojie J. Zhang79, Richard Y. Zhao80, Bing Zhou81, Lorenzo Galluzzi82–84,*, Guido Kroemer84–90,*, Frank Madeo1,26,*

In this review, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of yeast.

Burkholderia gladioli strain NGJ1 deploys a prophage tail-like protein for mycophagy

Rahul Kumar1, Sunil Kumar Yadav1, Durga Madhab Swain1 and Gopaljee Jha1

In this article, the authors comment on the study "A prophage tail-like protein is deployed by Burkholderia bacteria to feed on fungi" by Swain et al. (Nature Communications, 2017), discussing that a prophage tail-like protein (Bg_9562) is essential for mycophagy. The protein may help the bacteria to survive in certain ecological niches and, considering its broad-spectrum antifungal activity, may be potentially useful in biotechnological applications to control fungal diseases.

Ras signalling in pathogenic yeasts

Daniel R. Pentland1, Elliot Piper-Brown1, Fritz A. Mühlschlegel1,2 and Campbell W. Gourlay1

In this article Pentland et al. review the roles of Ras protein function and signalling in the major human yeast pathogens Candida albicans and Cryptococcus neoformans and discuss the potential for targeting Ras as a novel approach to anti-fungal therapy.

The logics of metabolic regulation in bacteria challenges biosensor-based metabolic engineering

Matthieu Jules1

In this article, the authors comment on the study "Molecular and Physiological Logics of the Pyruvate-Induced Response of a Novel Transporter in Bacillus subtilis" by Charbonnier et al. (mBio, 2017), which identified and characterized a pyruvate transport system in the Gram-positive (G+ve) bacterium Bacillus subtilis, a well-established biotechnological workhorse for the production of enzymes, fine chemicals and antibiotics.

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.