Vol. 05, 2018

Temporal analysis of the autophagic and apoptotic phenotypes in Leishmania parasites

Louise Basmaciyan¹, Laurence Berry², Julie Gros³, Nadine Azas³ and Magali Casanova³

This article details a comprehensive analysis of miltefosine-induced cell death and autophagy in Leishmania major, providing criteria for clear identification of apoptotic and autophagic cells, demonstrating the sequential nature of autophagy followed by apoptosis in nutrient-deprived conditions, and cautioning against using the generic kinase inhibitor staurosporine as a Leishmania apoptosis inducer, with the aim of improving the understanding of these processes and their targeting for new anti-leishmanial drugs.

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.

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

Stephen D. Willis¹, David C. Stieg¹, Kai Li Ong², Ravina Shah^1,3, Alexandra K. Strich^1,4, Julianne H. Grose² and Katrina F. Cooper¹

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

Kid Kohl¹, Haroun Zangger¹, Matteo Rossi¹, Nathalie Isorce¹, Lon-Fye Lye², Katherine L. Owens², Stephen M. Beverley², Andreas Mayer¹ and Nicolas Fasel¹

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

Patrick Van Dijck^1,2,‡, Jelmer Sjollema^3,‡, Bruno P.A. Cammue^4,5, Katrien Lagrou^6,7, Judith Berman⁸, Christophe d’Enfert⁹, David R. Andes^10,11, Maiken C. Arendrup^12-14, Axel A. Brakhage¹⁵, Richard Calderone¹⁶, Emilia Cantón¹⁷, Tom Coenye^18,19, 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. Pfaller^35,36, Gordon Ramage^19,37, Dominique Sanglard³⁸, Maurizio Sanguinetti³⁹, Isabel Spriet⁴⁰, Paul E. Verweij⁴¹, Adilia Warris⁴², Joost Wauters⁴³, Michael R. Yeaman⁴⁴, Sebastian A.J. Zaat⁴⁵, Karin Thevissen^4,*

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. Reinert^1,2, 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. Mojica^1,2

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.

Microbial wars: competition in ecological niches and within the microbiome

Maria A. Bauer¹, Katharina Kainz¹, Didac Carmona-Gutierrez¹ and Frank Madeo^1,2

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.

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

Rossella Avagliano Trezza^1,#, Janny van den Burg¹, Nico van den Oever¹ and Ben Distel^1,2

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 Bettiga^1,4

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 Staudacher^1,3, Gabriele Pradel² and Marcel Deponte^1,3

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.

Retroviral integration site selection: a running Gag?

Paul Lesbats^1,2,3 and Vincent Parissi^1,2,3

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 Flieger^1,#, 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 Coccetti^1,2, Raffaele Nicastro^1,3 and Farida Tripodi^1,2

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. Sewell^1,2, Min Han^1,2 and Bin Qi^1,2

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 Kerstens^1,2 and Patrick Van Dijck^1,2

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.

Microbial wars: competition in ecological niches and within the microbiome

Maria A. Bauer¹, Katharina Kainz¹, Didac Carmona-Gutierrez¹ and Frank Madeo^1,2

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, Jr^1,2,3

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.

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

December 11, 2017

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.

A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori

December 9, 2017

In this article, the authors comment on the study "Helicobacter pylori Employs a Unique Basolateral Type IV Secretion Mechanism for CagA Delivery" by Tegtmeyer et al. (Cell Host Microbe, 2017), discussing that the finding of a T4SS receptor suggests the presence of a sophisticated control mechanism for the injection of CagA and the possible impact of this novel signaling cascade on pathogenesis during infection with Helicobacter pylori.

Yeast quiescence exit swiftness is influenced by cell volume and chronological age

December 6, 2017

Quiescence exit swiftness is crucial not only for micro-organisms in competition for an environmental niche, such as yeast, but also for the maintenance of tissue homeostasis in multicellular species. Here, Laporte et al. explore the effect of replicative and chronological age on Saccharomyces cerevisiae quiescence exit efficiency. Overall, their data illustrate that the quiescent state is a continuum evolving with time, early and deep quiescence being distinguishable by the cell’s proficiency to re-enter the proliferation cycle.