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.

Next

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.

Next

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.

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.

A global view of substrate phosphorylation and dephosphorylation during budding yeast mitotic exit

Sandra A. Touati1 and Frank Uhlmann1

In this article, the authors comment on the study "Phosphoproteome dynamics during mitotic exit in budding yeast" by Touati (EMBO J, 2018) that described a time-resolved global phosphoproteome analysis during a cell cycle phase known as mitotic exit in budding yeast revealed the principles of phosphoregulation governing the ordered sequence of events such as spindle elongation, chromosome decondensation, and completion of cell division.

Gammaretroviruses tether to mitotic chromatin by directly binding nucleosomal histone proteins

Madushi Wanaguru1 and Kate N. Bishop1

In this article, the authors comment on the study "Murine leukemia virus p12 tethers the capsid-containing pre-integration complex to chromatin by binding directly to host nucleosomes in mitosis" by Wanaguruet al. (PLoS Pathog, 2018) that highlights the essential role of the gammaretroviral gag cleavage product, p12, at both early and late stages of the virus life cycle, particularly in the integration of the viral DNA into the host cell chromatin to form a provirus. It also emphasizes the recent findings regarding the N- and C-terminal domains of p12, revealing their direct binding to the viral capsid lattice and nucleosomal histone proteins, respectively, thus elucidating the mechanism by which p12 links the viral pre-integration complex to mitotic chromatin.

Methodologies for in vitro and in vivo evaluation of efficacy of antifungal and antibiofilm agents and surface coatings against fungal biofilms

Patrick Van Dijck1,2,‡, Jelmer Sjollema3,‡, Bruno P.A. Cammue4,5, Katrien Lagrou6,7, Judith Berman8, Christophe d’Enfert9, David R. Andes10,11, Maiken C. Arendrup12-14, Axel A. Brakhage15, Richard Calderone16, Emilia Cantón17, Tom Coenye18,19, Paul Cos20, Leah E. Cowen21, Mira Edgerton22, Ana Espinel-Ingroff23, Scott G. Filler24, Mahmoud Ghannoum25, Neil A.R. Gow26, Hubertus Haas27, Mary Ann Jabra-Rizk28, Elizabeth M. Johnson29, Shawn R. Lockhart30, Jose L. Lopez-Ribot31, Johan Maertens32, Carol A. Munro26, Jeniel E. Nett33, Clarissa J. Nobile34, Michael A. Pfaller35,36, Gordon Ramage19,37, Dominique Sanglard38, Maurizio Sanguinetti39, Isabel Spriet40, Paul E. Verweij41, Adilia Warris42, Joost Wauters43, Michael R. Yeaman44, Sebastian A.J. Zaat45, Karin Thevissen4,*

This article highlights the critical importance of accurate susceptibility testing methods and the discovery of novel antifungal and antibiofilm agents in combating invasive fungal infections associated with biofilm formation on medical devices, thereby emphasizing the need for advancements in medical mycology research to address these complex diseases.

Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks

Gabriele A. Fontana1, Julia K. Reinert1,2, Nicolas H. Thomä1, Ulrich Rass1

This review discusses the conserved mechanisms cells have evolved to protect DNA ends at chromosomal termini and DNA double-strand breaks (DSBs), focusing on the protein Rif1’s roles in telomere homeostasis and DSB repair in eukaryotes. It highlights the intriguing connection between Rif1's involvement in both telomere maintenance and DSB repair, and suggests that excluding end-processing factors may underlie Rif1's diverse biological functions at telomeres and chromosome breaks.

The CRISPR conundrum: evolve and maybe die, or survive and risk stagnation

Jesús García-Martínez1, Rafael D. Maldonado1, Noemí M. Guzmán1 and Francisco J. M. Mojica1,2

In this article García-Martínez et al. cover how the model bacterium Escherichia coli deals with CRISPR-Cas to tackle the major dilemma of evolution versus survival.

A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases

Soham Gupta1, Päivi Ylä-Anttila1, Maria G. Masucci1

In this article, the authors comment on the study "Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome" by Gupta et al. (PLoS Pathog, 2018), discussing the finding of a novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases.

Metabolic disharmony and sibling conflict mediated by T6SS

Vera Troselj1 and Daniel Wall1

In this article, the authors comment on the study "Physiological Heterogeneity Triggers Sibling Conflict Mediated by the Type VI Secretion System in an Aggregative Multicellular Bacterium" by Troselj et al. (MBio, 2018) discussing that M. xanthus uses T6SS to eliminate less fit cells from their population and identified toxic effector and cognate immunity protein (TsxEI) that mediates this sibling antagonism.

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.

Non-canonical regulation of glutathione and trehalose biosynthesis characterizes non-Saccharomyces wine yeasts with poor performance in active dry yeast production

January 26, 2018

Several yeast species, belonging to Saccharomyces and non-Saccharomyces genera, play fundamental roles during spontaneous must grape fermentation, and recent studies have shown that mixed fermentations, co-inoculated with S. cerevisiae and non-Saccharomyces strains, can improve wine organoleptic properties. Here, Gamero-Sandemetrio et al. present findings that non-canonical regulation of glutathione and trehalose biosynthesis could cause poor fermentative performance after active dry yeast (ADY) production, as it corroborates the corrective effect of antioxidant treatments, during biomass propagation, with both pure chemicals and food-grade argan oil.

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

January 16, 2018

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).

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

January 16, 2018

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

January 14, 2018

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

January 13, 2018

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

January 12, 2018

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

January 1, 2018

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

December 31, 2017

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.

Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes

December 28, 2017

Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. Saccharomyces cerevisiae has two FITM homologues and the presented results suggest that Scs3p and Yft2p as well as FITMs in general are lipid phosphatase/phosphotransferase (LPT) enzymes involved in an as yet unknown critical step in phospholipid metabolism.

Ras signalling in pathogenic yeasts

December 18, 2017

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.