Vol. 07, 2020

Maintaining phagosome integrity during fungal infection: do or die?

Mabel Yang¹, Glenn F.W. Walpole^1,2 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. Gross^2,3 and Albert Siryaporn^1,3

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 Bose^1,#, Shifu Aggarwal^1,#, Durg Vijai Singh^1,2 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 Tsuchikado^1,#, Satoshi Kami^1,#, 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. Clear^1,2,3, Glenn M. Manthey^1,2, Olivia Lewis^4,5, Isabelle Y. Lopez^4,6, Rossana Rico^4,7, Shannon Owens^8,9, M. Cristina Negritto¹⁰, Elise W. Wolf^10,11, Jason Xu^10,12, Nikola Kenjić¹³, J. Jefferson P. Perry¹³, Aaron W. Adamson¹⁴, Susan L. Neuhausen¹⁴, Adam M. Bailis^1,2,15

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 Martel^1,2, Cheng-Yeu Wu^1-3, Hsin-Hsin Peng^1,2,4, Yun-Fei Ko^2,5,6, Hung-Chi Yang⁷, John D. Young⁵ and David M. Ojcius^1,2,8

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.

Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage

Pedro Ortega¹, Desiré García-Pichardo¹, Marta San Martin-Alonso¹, Ana G. Rondón¹, Belén Gómez-González¹ and Andrés Aguilera¹

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

Gukui Chen¹ and Haihua Liang¹

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.

A multifunctional small RNA binding protein for sensing and signaling cell envelope precursor availability in bacteria

Muna A. Khan¹ and Boris Görke¹

This article relates to the study "Small RNA‐binding protein RapZ mediates cell envelope precursor sensing and signaling in Escherichia coli" by Khan et al. (EMBO J, 2020) that uncovers a complex regulatory network in E. coli where the RNA-binding protein RapZ functions as a sensor for GlcN6P, coordinating sRNA activity and a two-component system to maintain GlcN6P homeostasis and regulate cell envelope biosynthesis.

Sulforaphane alters the acidification of the yeast vacuole

Alexander Wilcox^1,#, Michael Murphy^1,#, Douglass Tucker^1,#, David Laprade¹, Breton Roussel¹, Christopher Chin², Victoria Hallisey¹, Noah Kozub¹, Abraham Brass² and Nicanor Austriaco¹

This study identifies vacuolar pH regulation as a key factor in sulforaphane (SFN) sensitivity, showing that SFN-induced cell death in yeast - and potentially in human cancer cells - is linked to its ability to raise vacuolar or lysosomal pH.

Regulation of anti-microbial autophagy by factors of the complement system

Christophe Viret¹, Aurore Rozières¹, Rémi Duclaux-Loras¹, Gilles Boschetti¹, Stéphane Nancey¹ and
Mathias Faure^1,2

This review explores emerging evidence that components of the complement system, beyond their traditional immune roles, modulate autophagy - particularly xenophagy - thereby influencing cell-autonomous antimicrobial responses during host-pathogen interactions.

Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids

Edruce Edouarzin¹, Connor Horn², Anuja Paudyal², Cunli Zhang¹, Jianyu Lu¹, Zongbo Tong¹, Guri Giaever³, Corey Nislow³, Raja Veerapandian², Duy H. Hua¹ and Govindsamy Vediyappan²

This study identifies (-)-drimenol as a potent broad-spectrum antifungal agent effective against multiple pathogenic fungi, including drug-resistant strains, and reveals its mechanism of action involves disruption of fungal membranes and targeting Crk1-related pathways, with potential for structural optimization to enhance efficacy.

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Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins

Mehdi Kabani¹

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.

Regulation of Cdc42 for polarized growth in budding yeast

Kristi E. Miller^1,2, Pil Jung Kang¹ and Hay-Oak Park¹

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

Tiziana Cervelli¹, Samuele Lodovichi¹, Francesca Bellè¹ and Alvaro Galli¹

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.

A novel c-di-GMP signal system regulates biofilm formation in Pseudomonas aeruginosa

Gukui Chen¹ and Haihua Liang¹

A multifunctional small RNA binding protein for sensing and signaling cell envelope precursor availability in bacteria

Muna A. Khan¹ and Boris Görke¹

Regulation of anti-microbial autophagy by factors of the complement system

Christophe Viret¹, Aurore Rozières¹, Rémi Duclaux-Loras¹, Gilles Boschetti¹, Stéphane Nancey¹ and
Mathias Faure^1,2

More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans

Chengjun Cao¹ and Chaoyang Xue^1,2

In this article, the authors comment on the study "A mechanosensitive channel governs lipid flippase-mediated echinocandin resistance in Cryptococcus neoformans" by Cao et al. (mBio, 2019), which uncovers a dual role for the lipid flippase subunit Cdc50 in Cryptococcus neoformans, linking lipid translocation and calcium signaling via its interaction with the mechanosensitive channel Crm1, thereby contributing to innate resistance against the antifungal drug caspofungin.

New insights in the mode of action of anti-leishmanial drugs by using chemical mutagenesis screens coupled to next-generation sequencing

Arijit Bhattacharya¹, Sophia Bigot², Prasad Kottayil Padmanabhan², Angana Mukherjee², Adriano Coelho³, Philippe Leprohon², Barbara Papadopoulou² and Marc Ouellette²

In this article, the authors comment on the study "Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania" by Bhattacharya et al. (Nat Commun, 2019), which introduces Mut-seq, a chemical mutagenesis and sequencing approach, to uncover drug resistance mechanisms in Leishmania, revealing links between lipid metabolism genes and miltefosine resistance, and a protein kinase involved in translation conferring paromomycin resistance.

Microfluidic techniques for separation of bacterial cells via taxis

Jyoti P. Gurung¹, Murat Gel^2,3 and Matthew A. B. Baker^1,3

Microfluidic tools, ideal for studying microbial motility due to their control over laminar flows at microscopic scales, enable precise analysis of various taxis behaviors and have advanced applications in synthetic biology, directed evolution, and medical microbiology.

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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 Madeo^1-3 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 Zimmermann^1,2, Katharina Kainz¹,
Sebastian J. Hofer¹, Guido Kroemer^3-7 and Frank Madeo^1,2,8

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.

Raman-based sorting of microbial cells to link functions to their genes

Kang Soo Lee¹, Michael Wagner^2,3 and Roman Stocker¹

In this article, the authors comment on the study "An automated Raman-based platform for the sorting of live cells by functional properties" by Lee et al. (Nat Microbiol, 2019), which presents a high-throughput optofluidic platform that integrates Raman microspectroscopy and microfluidics to accurately link microbial phenotypes to genotypes within complex communities, enabling efficient functional sorting and analysis of microbiome members.

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.

The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast

January 3, 2020

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.

Viral attenuation by Endonuclease G during yeast gametogenesis: insights into ancestral roles of programmed cell death?

December 17, 2019

Depletion of SNAP-23 and Syntaxin 4 alters lipid droplet homeostasis during Chlamydia infection

December 3, 2019

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

November 25, 2019

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

November 19, 2019

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.