Microreviews, Review
Mutagenesis by host antimicrobial peptides: insights into microbial evolution during chronic infections
Dominique H. Limoli and Daniel J. Wozniak
This article comments on work published by Limoli et al. ((PLoS Pathogens, 2014), which provides evidence that at subinhibitory levels, AMPs promote mutations in bacterial DNA, which enhance bacterial survival.
Where antibiotic resistance mutations meet quorum-sensing
Rok Krašovec1, Roman V. Belavkin2, John A.D. Aston3, Alastair Channon4, Elizabeth Aston4, Bharat M. Rash1, Manikandan Kadirvel5,6, Sarah Forbes6, and Christopher G. Knight1
This article comments on work published by Krašovec et al. (Nat Comm, 2014), which found that the modulation of de novo mutation to promote antibiotic resistance depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress).
Sphingolipids and mitochondrial function, lessons learned from yeast
Pieter Spincemaille1, Bruno P.A. Cammue1,2 and Karin Thevissen1
This article reviews recent research showing that Saccharomyces cerevisiae is an invaluable model to investigate sphingolipids as signaling molecules in modulating mitochondrial function, but can also be used as a tool to further enhance our current knowledge on sphingolipids and mitochondria in mammalian cells.
Genome evolution in yeast reveals connections between rare mutations in human cancer
Xinchen Teng1,2 and J. Marie Hardwick2
This article comments on work published by Teng et al. (Mol Cell, 2013), which, using the yeast knockout collections, provides hard evidence that single gene deletions/mutations in most non-essential genes can drive the selection for cancer-like mutations.
Decoding the biosynthesis and function of diphthamide, an enigmatic modification of translation elongation factor 2 (EF2)
Raffael Schaffrath and Michael J. R. Stark
This article comments on work published by Uthman et al. (PLoS Genet, 2013), which suggests that Dph5 has a novel role as an EF2 inhibitor that affects cell growth when diphthamide synthesis is blocked or incomplete and shows that diphthamide promotes the accuracy of EF2 performance during translation.
Autophagy extends lifespan via vacuolar acidification
Christoph Ruckenstuhl1, Christine Netzberger1, Iryna Entfellner1, Didac Carmona-Gutierrez1, Thomas Kickenweiz1, Slaven Stekovic1, Christina Gleixner1, Christian Schmid1, Lisa Klug1, Ivan Hajnal1, Alice G. Sorgo1, Tobias Eisenberg1, Sabrina Büttner1, Guillermo Marin͂o2-4, Rafal Koziel5, Christoph Magnes6, Frank Sinner6,7, Thomas R. Pieber6,7, Pidder Jansen-Dürr5, Kai-Uwe Fröhlich1, Guido Kroemer2,3,8-11, and Frank Madeo1
This article comments on work published by Ruckenstuhl et al. (PLoS Genet, 2014), which uses Saccharomyces cerevisiae to show that autophagy promotes lifespan extension upon MetR and requires the subsequent stimulation of vacuolar acidification, while it is epistatic to the equally autophagy-dependent anti-aging pathway triggered by TOR1 inhibition or deletion.
When less is more: hormesis against stress and disease
Andreas Zimmermann1, Maria A. Bauer1, Guido Kroemer2-5, Frank Madeo1 and Didac Carmona-Gutierrez1
This article condenses the conceptual and potentially therapeutic importance of hormesis by providing a short overview of current evidence in favor of the cytoprotective impact of hormesis, as well as of its underlying molecular mechanisms.
Morphed and moving: TNFα-driven motility promotes cell dissemination through MAP4K4-induced cytoskeleton remodeling
Min Ma1,2 and Martin Baumgartner1
This article comments on work published by Ma and Baumgartner (PLoS Patho, 2014), which investigated Theileria parasite control of host cell motile properties in the context of inflammatory signaling.
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.
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.
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.