Vol. 05, 2018

A versatile plasmid system for reconstitution and analysis of mammalian ubiquitination cascades in yeast

Rossella Avagliano Trezza1,#, Janny van den Burg1, Nico van den Oever1 and Ben Distel1,2

In this article Avagliano Trezza et al. describe a versatile vector system that allows the reconstitution of specific ubiquitination cascades in the model eukaryote Saccharomyces cerevisae (baker’s yeast) that provides a versatile tool to study complex post-translational modifications in a cellular setting.

Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae : biophysical mechanisms and implications for acetic acid tolerance

Lina Lindahl1, Samuel Genheden2, Fábio Faria-Oliveira1, Stefan Allard3, Leif A. Eriksson2, Lisbeth Olsson1, Maurizio Bettiga1,4

Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes.

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica

Jannell V. Bazurto1, Stephen P. Dearth2, Eric D. Tague2, Shawn R. Campagna2 and Diana M. Downs1

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

Cletus A. Wezena1, Romy Alisch1, Alexandra Golzmann2, Linda Liedgens1, Verena Staudacher1,3, Gabriele Pradel2 and Marcel Deponte1,3

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.

Previous

A versatile plasmid system for reconstitution and analysis of mammalian ubiquitination cascades in yeast

Rossella Avagliano Trezza1,#, Janny van den Burg1, Nico van den Oever1 and Ben Distel1,2

In this article Avagliano Trezza et al. describe a versatile vector system that allows the reconstitution of specific ubiquitination cascades in the model eukaryote Saccharomyces cerevisae (baker’s yeast) that provides a versatile tool to study complex post-translational modifications in a cellular setting.

Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae : biophysical mechanisms and implications for acetic acid tolerance

Lina Lindahl1, Samuel Genheden2, Fábio Faria-Oliveira1, Stefan Allard3, Leif A. Eriksson2, Lisbeth Olsson1, Maurizio Bettiga1,4

Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes.

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica

Jannell V. Bazurto1, Stephen P. Dearth2, Eric D. Tague2, Shawn R. Campagna2 and Diana M. Downs1

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

Cletus A. Wezena1, Romy Alisch1, Alexandra Golzmann2, Linda Liedgens1, Verena Staudacher1,3, Gabriele Pradel2 and Marcel Deponte1,3

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.

Previous

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.

Gammaretroviruses tether to mitotic chromatin by directly binding nucleosomal histone proteins

July 24, 2018

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.

Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

June 25, 2018

This article explores the response of eukaryotic cells to environmental stress, highlighting the role of the conserved cyclin C-Cdk8 kinase in determining pro-survival or pro-death programs. Specifically, it discusses how oxidative stress triggers the destruction of Med13 by the SCFGrr1 ubiquitin ligase, releasing cyclin C to promote mitochondrial fission and cell death in Saccharomyces cerevisiae. Additionally, it reveals that the AMP kinase Snf1 activates a separate degron in Med13, contributing to the complex regulation of Med13 degradation following H2O2 stress through the coordination of the cell wall integrity and MAPK pathways.

Importance of polyphosphate in the Leishmania life cycle

June 22, 2018

This article explores the importance of polyphosphate (polyP) in Leishmania parasites, emphasizing the role of the polyP polymerase VTC4 and its impact on parasite survival at higher temperatures. Additionally, it discusses the effects of VTC4 knockout in mouse infections, noting a delay in lesion formation and strong pathology in L. major VTC4 knockout, without confirmation through complementation and no alteration in L. guyanensis infections in mice with VTC4 knockdown.

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

June 14, 2018

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

May 17, 2018

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

May 16, 2018

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.

Microbial wars: competition in ecological niches and within the microbiome

May 7, 2018

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.

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

April 11, 2018

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

April 4, 2018

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.

Antagonism between salicylate and the cAMP signal controls yeast cell survival and growth recovery from quiescence

March 26, 2018

This article describes the effects of salicylate, the main metabolite of aspirin, on S. cerevisiae cells. It outlines how salicylate influences glucose transport, sugar phosphate biosynthesis, and apoptosis, particularly in MnSOD-deficient cells. Furthermore, it emphasizes the significant impact of salicylate on the exit from a quiescent state, inhibiting growth recovery and viability in long-term stationary phase cells. The passage also discusses the potential therapeutic implications of understanding the antagonistic relationship between cAMP and salicylate in targeting quiescent cancer cells with stem-like properties.