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.

Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae

Anthony Arlia-Ciommo#, Anna Leonov#, Amanda Piano#, Veronika Svistkova# and Vladimir I. Titorenko

This article critically analyzes recent advances in the understanding of cell-autonomous mechanisms of chronological aging in the budding yeast Saccharomyces cerevisiae. It proposes a concept of a biomolecular network underlying the chronology of cellular aging in yeast, whichposits that such network progresses through a series of lifespan checkpoints.

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.

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When the pandemic opts for the lockdown: Secretion system evolution in the cholera bacterium

February 18, 2021

This article comments on work published by Santoriello et al. (Nat Comm, 2020), which demonstrates that the T6SS island Auxiliary Cluster 3 (Aux3) is unique to pandemic strains of V. cholerae.

Maintaining phagosome integrity during fungal infection: do or die?

December 3, 2020

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

October 8, 2020

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.

Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum

September 16, 2020

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.

A new role for proteins subunits of RNase P: stabilization of the telomerase holoenzyme

June 17, 2020

This article refers to the study "Stability and Nuclear Localization of Yeast Telomerase Depend on Protein Components of RNase P/MRP", by Garcia et al. (Nat Commun, 2020), showing that 3 essential proteins in Saccharomyces cerevisiae are vital for telomerase assembly and nuclear localization. In their mutants, telomerase is less mature, and telomeres are shorter. TLC1 is properly folded but remains in the cytoplasm, rather than moving to the nucleus, where it maintains telomeres.

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.

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.

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.

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