Review, Reviews

Out with the old: Hsp90 finds amino acid residue more useful than co-chaperone protein

Abbey D. Zuehlke1 and Leonard Neckers1

This article comments on work published by Zuehlke et al (Nat Commun, 2017), which demonstrates that the function of one co-chaperone in yeast is replaced by posttranslational modification (PTM) of a single amino acid within Hsp90 in higher eukaryotes.

Having your cake and eating it – Staphylococcus aureus small colony variants can evolve faster growth rate without losing their antibiotic resistance

Gerrit Brandis1, Sha Cao1, Douglas L. Huseby1 and Diarmaid Hughes1

This article comments on work published by Cao et al. (mBio, 2027), which shows that Staphylococcus aureus can produce small colony variants (SCVs) that are challenging to detect and lead to persistent infections due to mutations affecting respiration and ATP production, with recent findings indicating various evolutionary paths for SCVs to increase growth rate while maintaining antibiotic resistance, suggesting greater adaptability and clinical challenge.

Integrative metabolomics as emerging tool to study autophagy regulation

Sarah Stryeck1, Ruth Birner-Gruenberger2, Tobias Madl1,*

This review summarizes the advancements in metabolomics, particularly using NMR spectroscopy and mass spectrometry, and its increasing role in biological research, offering insights into autophagy regulation with a focus on key metabolites, recent studies, and future prospects in elucidating complex regulatory mechanisms of autophagy and related diseases.

The interplay between transcription and mRNA degradation in Saccharomyces cerevisiae

Subhadeep Das1, Debasish Sarkar2 and Biswadip Das1

This review summarizes how the integration of mRNA synthesis and degradation, mediated by specialized promoters and "coordinators," shapes the cellular transcriptome and plays a significant role in regulating gene expression profiles in various biological processes and potentially enhances evolutionary rates.

Inhibitors of glycosomal protein import provide new leads against trypanosomiasis

Vishal C. Kalel1, Leonidas Emmanouilidis2,3, Maciej Dawidowski2,3,4, Wolfgang Schliebs1, Michael Sattler2,3, Grzegorz M. Popowicz2,3, Ralf Erdmann1

This article comments on work published by Dawidowski et al. (Science, 2017), which provides the grounds for further development of the glycosome inhibitors into clinical candidates and validates the parasite protein-protein interactions as drug targets.

Impact of the host on Toxoplasma stage differentiation

Carsten G.K. Lüder1 and Taibur Rahman1

This review summarizes how Toxoplasma gondii transitions from an acute to a chronic infection in warm-blooded animals and humans through a developmental switch influenced by host cell physiology, which determines parasite persistence mainly in neural and muscular tissues.

Chlamydia and mitochondria – an unfragmented relationship

Suvagata Roy Chowdhury1 and Thomas Rudel1

This article comments on work published by Chowdhury et al (J Cell Biol, 2017), which demonstrated that Chlamydia infection induces and requires an upregulation of the host miRNA, miR-30c-5p (miR-30c) to ameliorate infection induced stress on the host mitochondrial architecture and hinders induction of apoptosis.

Protein aggregation triggers a declining libido in elder yeasts that still have a lust for life

Fabrice Caudron

This article comments on work published by Schlissel et al (Science 2017), showing that aging in yeast does not lead to the expected loss of heterochromatin silencing due to Sir2 inactivity, but rather to reduced mating pheromone sensitivity caused by the aggregation of the RNA-binding protein Whi3, which can be reversed by eliminating Whi3's polyglutamine domain.

Post-transcriptional regulation of ribosome biogenesis in yeast

Isabelle C. Kos-Braun and Martin Koš

Microorganisms adapt to environmental changes by regulating their metabolism, and one key survival strategy is to decrease energy use during adverse conditions by halting ribosome production, with recent findings showing yeast can switch between pre-rRNA processing pathways in response to environmental shifts, adding complexity to ribosome biogenesis regulation.

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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.

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.

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.

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.

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.

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.

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.

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