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.

Next

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.

Next

Influence of delivery and feeding mode in oral fungi colonization – a systematic review

Maria Joao Azevedo1,2,3,4, Maria de Lurdes Pereira1,5, Ricardo Araujo2,3,6, Carla Ramalho3,7,8, Egija Zaura4 and Benedita Sampaio-Maia1,2,3

A systematic review of oral fungal colonization in infants found that while breastfeeding did not significantly affect the oral mycobiome, vaginal delivery was associated with higher oral yeast colonization, particularly of Candida albicans.

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.

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.

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

Kang Soo Lee1, Michael Wagner2,3 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.

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

April 15, 2020

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

March 20, 2020

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

March 19, 2020

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

March 12, 2020

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.

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

February 20, 2020

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.

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

February 10, 2020

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.

Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae

February 5, 2020

This study introduces GFP-based transcriptional reporters driven by a calcineurin-dependent response element, enabling real-time monitoring of calcineurin activity in live yeast cells for studying stress responses, aging, and antifungal drug screening.

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

January 21, 2020

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

January 15, 2020

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.

Influence of delivery and feeding mode in oral fungi colonization – a systematic review

January 7, 2020

A systematic review of oral fungal colonization in infants found that while breastfeeding did not significantly affect the oral mycobiome, vaginal delivery was associated with higher oral yeast colonization, particularly of Candida albicans.