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 Shah1,3, Alexandra K. Strich1,4, 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 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.
Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes
Matthew J Hayes1, Vineet Choudhary2, Namrata Ojha2, John JH Shin3, Gil-Soo Han4, George M. Carman4, Christopher JR Loewen3, William A Prinz2 and Timothy P Levine1
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
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.
A novel basolateral type IV secretion model for the CagA oncoprotein of Helicobacter pylori
Silja Wessler1 and Steffen Backert2
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
Damien Laporte1, Laure Jimenez1, Laëtitia Gouleme1, Isabelle Sagot1
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.
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.
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.
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.
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.
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.
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.