Vol. 07, 2020
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.
Sulforaphane alters the acidification of the yeast vacuole
Alexander Wilcox1,#, Michael Murphy1,#, Douglass Tucker1,#, 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 Faure1,2
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.
More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans
Chengjun Cao1 and Chaoyang Xue1,2
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.
Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae
Jutta Diessl1, Arpita Nandy1, Christina Schug1, Lukas Habernig1 and Sabrina Büttner1,2
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.
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.
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.
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.
Regulation of Cdc42 for polarized growth in budding yeast
Kristi E. Miller1,2, 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.
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.
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. Miller1,2, 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
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.
Regulation of anti-microbial autophagy by factors of the complement system
Christophe Viret1, Aurore Rozières1, Rémi Duclaux-Loras1, Gilles Boschetti1, Stéphane Nancey1 and
Mathias Faure1,2
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.
More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans
Chengjun Cao1 and Chaoyang Xue1,2
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 Gel2,3 and Matthew A. B. Baker1,3
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.
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.
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.
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.
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.