Vol. 07, 2020
Maintaining phagosome integrity during fungal infection: do or die?
Mabel Yang1, Glenn F.W. Walpole1,2 and Johannes Westman1
This article refers to the paper "Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection" by Westman et al. (Cell Host Microbe, 2020), which shows that macrophages respond to pathogen growth by expanding the phagosome membrane through a calcium-dependent mechanism involving lysosome insertion, maintaining membrane integrity and preventing rupture.
A novel antibacterial strategy: histone and antimicrobial peptide synergy
Leora Duong1, Steven P. Gross2,3 and Albert Siryaporn1,3
This article refers to the study "Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization" by Doolin et al. (Nat Comm, 2020) that shows that histones enhance the antimicrobial activity of peptides, disrupt bacterial membranes, and inhibit transcription, offering new insights into natural antimicrobial mechanisms.
Extracellular vesicles: An emerging platform in gram-positive bacteria
Swagata Bose1,#, Shifu Aggarwal1,#, Durg Vijai Singh1,2 and Narottam Acharya1
Extracellular vesicles (EVs) are secreted by both pathogenic and non-pathogenic bacteria to transfer biomolecules and facilitate intercellular communication. While EV secretion in gram-negative bacteria is well understood, less is known about gram-positive bacteria. This review explores the role of EVs involved in bacterial competition, survival, immune evasion, and infection of gram-positive bacteria and compares them to gram-negative counterparts.
Structural insights into the architecture and assembly of eukaryotic flagella
Narcis-Adrian Petriman1 and Esben Lorentzen1
Cilia and flagella are key structures in motility and signaling. This review highlights recent findings of cryo-EM studies that have mapped the structure of axonemal microtubules in Chlamydomonas reinhardtii, revealing over 30 associated proteins as well as recent researcht which focused on the trafficking complexes that transport components between the cell body and cilium.
Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
Jack D. Adderley1 and Christian Doerig1
This article refers to the study "Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention" by Adderley et al. (Nat Commun, 2020) that investigates how Plasmodium falciparum malaria parasites influence red blood cells. By tracking hanges in over 800 human proteins at different parasite stages they confirmed activation of the PAK-MEK pathway and discovered significant changes, particularly during the trophozoite stage. This suggests that kinases activated by the infection could be targeted for new antimalarial therapies.
Novobiocin inhibits membrane synthesis and vacuole formation of Enterococcus faecalis protoplasts
Rintaro Tsuchikado1,#, Satoshi Kami1,#, Sawako Takahashi1 and Hiromi Nishida1
In this study Tsuchikado et al. show that DNA replication is crucial for plasma membrane biosynthesis and vacuole formation in Enterococcus faecalis protoplasts. Novobiocin inhibits DNA replication, blocking cell enlargement and vacuole formation. Extended treatment prevents re-enlargement after removal.
Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast
Alissa D. Clear1,2,3, Glenn M. Manthey1,2, Olivia Lewis4,5, Isabelle Y. Lopez4,6, Rossana Rico4,7, Shannon Owens8,9, M. Cristina Negritto10, Elise W. Wolf10,11, Jason Xu10,12, Nikola Kenjić13, J. Jefferson P. Perry13, Aaron W. Adamson14, Susan L. Neuhausen14, Adam M. Bailis1,2,15
RAD52 is a key protein in DNA repair and suppresses DNA damage in yeast; however, certain variants affecting BRCA2 mutations fail to correct HRR defects. This suggests that HsRAD52 aids multiple DNA repair mechanisms and could be targeted for use in treating BRCA2-deficient cancers.
Plant and fungal products that extend lifespan in Caenorhabditis elegans
Jan Martel1,2, Cheng-Yeu Wu1-3, Hsin-Hsin Peng1,2,4, Yun-Fei Ko2,5,6, Hung-Chi Yang7, John D. Young5 and David M. Ojcius1,2,8
Caenorhabditis elegans' lifespan is extended by plant and fungal extracts activating pathways like autophagy and mitochondrial biogenesis. Low to moderate concentrations promote longevity, while high doses are harmful. This review explores the health benefits of these substances in humans.
Systematic analysis of nuclear gene function in respiratory growth and expression of the mitochondrial genome in S. cerevisiae
Maria Stenger1, Duc Tung Le1, Till Klecker1 and Benedikt Westermann1
Using yeast Saccharomyces cerevisiae, the authors identified 254 nuclear genes essential for respiratory growth and 12 required for viability without mtDNA. They also found 176 genes involved in mitochondrial protein synthesis and mtDNA maintenance, offering a comprehensive view of the processes supporting oxidative phosphorylation.
The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast
Paula R. Georgescu1, Matías Capella1, Sabine Fischer-Burkart1 and Sigurd Braun1
This study reveals that the loss of heterochromatin silencing in Set2-deficient cells is due to unrestrained Mst2C activity, highlighting the need for spatially restricted chromatin-modifying enzymes to maintain distinct chromatin states.
Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection
Tiago Monteiro-Brás1,2,3, Jordan Wesolowski1 and Fabienne Paumet1
This study reveals that the plasma membrane SNARE proteins SNAP-23 and Syntaxin 4 are crucial for Chlamydia trachomatis development by regulating lipid droplet homeostasis and supporting the formation of infectious progeny within host cells.
The role of Lactobacillus species in the control of Candida via biotrophic interactions
Isabella Zangl1, Ildiko-Julia Pap2, Christoph Aspöck2 and Christoph Schüller1,3
Microbial communities, including Candida and Lactobacillus species, play a crucial role in human health, particularly in the context of mucosal infections, but our understanding of their interactions and effects is still incomplete due to the variability of species and isolates as well as the complexity of the human host.
Yeast can express and assemble bacterial secretins in the mitochondrial outer membrane
Janani Natarajan1, Anasuya Moitra1, Sussanne Zabel1,§, Nidhi Singh2, Samuel Wagner2,3 and Doron Rapaport1
Secretins, essential components of bacterial secretion systems, can be expressed in yeast and show differential dependencies on mitochondrial import and assembly factors for membrane integration, suggesting diverse pathways for their assembly into the bacterial outer membrane.
Maintaining phagosome integrity during fungal infection: do or die?
Mabel Yang1, Glenn F.W. Walpole1,2 and Johannes Westman1
This article refers to the paper "Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection" by Westman et al. (Cell Host Microbe, 2020), which shows that macrophages respond to pathogen growth by expanding the phagosome membrane through a calcium-dependent mechanism involving lysosome insertion, maintaining membrane integrity and preventing rupture.
A novel antibacterial strategy: histone and antimicrobial peptide synergy
Leora Duong1, Steven P. Gross2,3 and Albert Siryaporn1,3
This article refers to the study "Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization" by Doolin et al. (Nat Comm, 2020) that shows that histones enhance the antimicrobial activity of peptides, disrupt bacterial membranes, and inhibit transcription, offering new insights into natural antimicrobial mechanisms.
Extracellular vesicles: An emerging platform in gram-positive bacteria
Swagata Bose1,#, Shifu Aggarwal1,#, Durg Vijai Singh1,2 and Narottam Acharya1
Extracellular vesicles (EVs) are secreted by both pathogenic and non-pathogenic bacteria to transfer biomolecules and facilitate intercellular communication. While EV secretion in gram-negative bacteria is well understood, less is known about gram-positive bacteria. This review explores the role of EVs involved in bacterial competition, survival, immune evasion, and infection of gram-positive bacteria and compares them to gram-negative counterparts.
Structural insights into the architecture and assembly of eukaryotic flagella
Narcis-Adrian Petriman1 and Esben Lorentzen1
Cilia and flagella are key structures in motility and signaling. This review highlights recent findings of cryo-EM studies that have mapped the structure of axonemal microtubules in Chlamydomonas reinhardtii, revealing over 30 associated proteins as well as recent researcht which focused on the trafficking complexes that transport components between the cell body and cilium.
Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
Jack D. Adderley1 and Christian Doerig1
This article refers to the study "Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention" by Adderley et al. (Nat Commun, 2020) that investigates how Plasmodium falciparum malaria parasites influence red blood cells. By tracking hanges in over 800 human proteins at different parasite stages they confirmed activation of the PAK-MEK pathway and discovered significant changes, particularly during the trophozoite stage. This suggests that kinases activated by the infection could be targeted for new antimalarial therapies.
Plant and fungal products that extend lifespan in Caenorhabditis elegans
Jan Martel1,2, Cheng-Yeu Wu1-3, Hsin-Hsin Peng1,2,4, Yun-Fei Ko2,5,6, Hung-Chi Yang7, John D. Young5 and David M. Ojcius1,2,8
Caenorhabditis elegans' lifespan is extended by plant and fungal extracts activating pathways like autophagy and mitochondrial biogenesis. Low to moderate concentrations promote longevity, while high doses are harmful. This review explores the health benefits of these substances in humans.
Lipid droplet biogenesis from specialized ER subdomains
Vineet Choudhary1 and Roger Schneiter2
This article refers to the paper "Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis" by Choudhary et al. (J Cell Biol, 2020), which deals with the formation of lipid droplets (LDs) at specific ER sites marked by the proteins Fld1 and Nem1. These proteins recruit enzymes such as Lro1 and Dga1 to initiate fat storage. Together, Fld1 and Nem1 define where LDs form by organising key proteins and lipids needed for their biogenesis.
From the Uncharacterized Protein Family 0016 to the GDT1 family: Molecular insights into a newly-characterized family of cation secondary transporters
Louise Thines1, Jiri Stribny1 and Pierre Morsomme1
This review outlines how the formerly uncharacterized UPF0016 family, now known as the Gdt1 family, plays key roles in cation transport - especially Mn²⁺ - across species from bacteria to humans. These proteins are crucial for processes like glycosylation, photosynthesis, and calcium signaling, with functions linked to their localization in membranes such as the Golgi, chloroplast, and plasma membrane and by that highlighting their evolutionary conservation and physiological relevance, offering insights into their shared and distinct features across organisms.
A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds
Meirong Song1 and Kui Zhu1
This article refers to the study "A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens" by Song et al. (Nat Microbiol, 2020), which deals with the growing threat of antibiotic resistance, with few new drugs being developed for decades. The study found that the peptide SLAP-S25 enhances the efficacy of several antibiotics against resistant Gram-negative bacteria by disrupting their membranes, thereby increasing drug uptake. This suggests that bacterial membranes are promising targets for new antibiotic adjuvants.
Regulation of the mitochondrial permeability transition pore and its effects on aging
Damiano Pellegrino-Coppola1
Aging is linked to mitochondrial function, with the mitochondrial permeability transition pore (mPTP) playing a key role. Yeast is a useful model for studying how mPTP affects cell survival, aging, and related diseases.
Fungal infections in humans: the silent crisis
Katharina Kainz1, Maria A. Bauer1, Frank Madeo1-3 and Didac Carmona-Gutierrez1
This article highlights the growing global threat of fungal infections - exacerbated by rising drug resistance and medical practices - and emphasizes the urgent need for intensified research to develop more effective antifungal strategies.
Digesting the crisis: autophagy and coronaviruses
Didac Carmona-Gutierrez1, Maria A. Bauer1, Andreas Zimmermann1,2, Katharina Kainz1,
Sebastian J. Hofer1, Guido Kroemer3-7 and Frank Madeo1,2,8
This article reviews the multifaceted role of autophagy in antiviral defense and highlights how coronaviruses, including SARS-CoV-2, interact with this pathway, raising the possibility that targeting autophagy could offer novel therapeutic strategies against COVID-19.
Lipid droplet biogenesis from specialized ER subdomains
June 16, 2020
This article refers to the paper "Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis" by Choudhary et al. (J Cell Biol, 2020), which deals with the formation of lipid droplets (LDs) at specific ER sites marked by the proteins Fld1 and Nem1. These proteins recruit enzymes such as Lro1 and Dga1 to initiate fat storage. Together, Fld1 and Nem1 define where LDs form by organising key proteins and lipids needed for their biogenesis.
From the Uncharacterized Protein Family 0016 to the GDT1 family: Molecular insights into a newly-characterized family of cation secondary transporters
June 15, 2020
This review outlines how the formerly uncharacterized UPF0016 family, now known as the Gdt1 family, plays key roles in cation transport - especially Mn²⁺ - across species from bacteria to humans. These proteins are crucial for processes like glycosylation, photosynthesis, and calcium signaling, with functions linked to their localization in membranes such as the Golgi, chloroplast, and plasma membrane and by that highlighting their evolutionary conservation and physiological relevance, offering insights into their shared and distinct features across organisms.
A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds
June 15, 2020
This article refers to the study "A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens" by Song et al. (Nat Microbiol, 2020), which deals with the growing threat of antibiotic resistance, with few new drugs being developed for decades. The study found that the peptide SLAP-S25 enhances the efficacy of several antibiotics against resistant Gram-negative bacteria by disrupting their membranes, thereby increasing drug uptake. This suggests that bacterial membranes are promising targets for new antibiotic adjuvants.
Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins
June 2, 2020
This article relates to the study "Glucose availability dictates the export of the soluble and prion forms of Sup35p via periplasmic or extracellular vesicles" by Kabani et al. (Mol Microbiol, 2020) that provides compelling evidence that yeast prions, such as Sup35p in its infectious [PSI⁺] state, can be exported via both extracellular vesicles (EVs) and periplasmic vesicles (PVs), with this export being modulated by environmental glucose levels. The discovery that prion particles are released in high amounts through PVs during glucose starvation adds a new dimension to our understanding of prion transmission and opens up fascinating possibilities for exploring vesicle-mediated spread of protein aggregates in neurodegenerative diseases using yeast as a model system.
Fungal infections in humans: the silent crisis
June 1, 2020
This article highlights the growing global threat of fungal infections - exacerbated by rising drug resistance and medical practices - and emphasizes the urgent need for intensified research to develop more effective antifungal strategies.
Regulation of Cdc42 for polarized growth in budding yeast
May 19, 2020
This review highlights how studies in budding yeast have revealed a biphasic mechanism of Cdc42 activation that governs cell polarity establishment, with implications for understanding similar processes in mammalian cells and the role of Cdc42 in aging.
Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes
May 18, 2020
This article highlights how the genetic tractability and conserved DNA repair pathways of yeast make it a powerful system for functionally characterizing human cancer-associated variants in DNA repair genes, aiding in risk assessment and therapeutic decision-making.
Digesting the crisis: autophagy and coronaviruses
May 4, 2020
This article reviews the multifaceted role of autophagy in antiviral defense and highlights how coronaviruses, including SARS-CoV-2, interact with this pathway, raising the possibility that targeting autophagy could offer novel therapeutic strategies against COVID-19.
Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage
April 24, 2020
This study reveals that conserved residues H3E73 and H4E53 in histones H3 and H4 play a crucial role in maintaining genome stability. Mutations at these sites increase recombinogenic DNA damage, likely due to replication-associated issues rather than transcriptional activity, highlighting their importance in DNA damage prevention and repair.
A novel c-di-GMP signal system regulates biofilm formation in Pseudomonas aeruginosa
April 23, 2020
This article relates to the study "The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa" by Chen et al. (EMBO J, 2020) that reveals a novel signaling network encoded by the siaABCD operon in Pseudomonas aeruginosa that regulates biofilm and aggregate formation by controlling the diguanylate cyclase activity of SiaD through phosphorylation-dependent interactions with SiaC, highlighting a potential antimicrobial target.
Viral attenuation by Endonuclease G during yeast gametogenesis: insights into ancestral roles of programmed cell death?
Jie Gao1, Sabrina Chau1 and Marc D. Meneghini1
This article relates to the study "Meiotic viral attenuation through an ancestral apoptotic pathway" by Gao et al. (Proc Natl Acad Sci, 2019), which shows that programmed cell death may have evolved as a viral defence mechanism, as demonstrated by yeast studies showing that the mitochondrial nuclease Nuc1 translocates to the cytosol during meiosis to attenuate dsRNA viruses, linking viral control to meiotic cell death processes.