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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Role of pheromone recognition systems in creating new species of fission yeast

March 11, 2019

This article comments on work published by Seike at al. (PloS Biol., 2019), which demonstrated an “asymmetric” pheromone recognition system in the fission yeast Schizosaccharomyces pombe.

Imbalance in gut microbes from babies born to obese mothers increases gut permeability and myeloid cell adaptations that provoke obesity and NAFLD

December 19, 2018

This article comments on work published by Soderborg et al. (Nat Commun, 2018), which demonstrates a causative role of early life microbiome dysbiosis in infants born to mothers with obesity in novel pathways that promote developmental programming of NAFLD.

Retroviral integration site selection: a running Gag?

November 19, 2018

In this article, the authors comment on the study "Structural basis for spumavirus GAG tethering to chromatin" by Lesbats et al. (Proc Natl Acad Sci, 2018) that revealed that the Gag protein of the spumaretrovirus prototype foamy virus (PFV) directly interacts with the nucleosome acidic patch, acting as a chromatin tether, and its disruption leads to delocalization of viral particles and integration sites, shedding light on the importance of retroviral structural proteins in the selection of integration sites.

Insights into the host-pathogen interaction: C. albicans manipulation of macrophage pyroptosis

November 12, 2018

In this article, the authors comment on the study "High-Throughput Screening Identifies Genes Required for Candida albicans Induction of Macrophage Pyroptosis" by O’Meara et al. (MBio, 2018) that provides a comprehensive analysis of the genetic circuitry in both Candida albicans and host macrophages that leads to pyroptosis, revealing the impact of altered pyroptosis on infection, the role of pyroptosis in facilitating neutrophil accumulation at the site of C. albicans infection, and the decoupling of inflammasome priming and activation in the response to C. albicans infection, thus shedding new light on the factors governing the outcomes of this interaction.

A comparative approach to decipher intestinal animal-microbe associations

October 31, 2018

In this article, the authors comment on the study "Chitin-based barrier immunity and its loss predated mucus-colonization by indigenous gut microbiota" by Nakashima et al. (Nat Commun, 2018) that used comparative analyses of chordates to investigate the development of animal-microbe associations, suggesting that microbial colonization of the mucus layer over mammalian gastrointestinal epithelium was established upon the loss of ancestral chitin-based barrier immunity, providing insights into the establishment of these associations in an evolutionary context.

An unexpected benefit from E. coli: how enterobactin benefits host health

September 28, 2018

In this article, the authors comment on the study "Microbial Siderophore Enterobactin Promotes Mitochondrial Iron Uptake and Development of the Host via Interaction with ATP Synthase" by Qi et al. (Cell, 2018) that uncovered a surprising role for the Escherichia coli-produced siderophore enterobactin (Ent) in facilitating iron uptake by the host, marking a major shift in the understanding of its function and indicating potential new benefits from commensal bacteria in aiding the host's iron homeostasis.

Toxin release mediated by the novel autolysin Cwp19 in Clostridium difficile

August 10, 2018

In this article, the authors comment on the study "Cwp19 is a novel lytic transglycosylase involved in stationary-phase autolysis resulting in toxin release in Clostridium difficile" by Wydau-Dematteis (MBio, 2018) that characterizes a novel peptidoglycan hydrolase, Cwp19, in Clostridioides difficile, highlighting its glucose-dependent mediation of toxins secretion and suggesting a potential role in the pathogenesis of this bacterium, contributing to the understanding of these enzymes in C. difficile and their implication in pathogenicity.

Escherichia coli hijack Caspr1 receptor to invade cerebral vascular and neuronal hosts

August 7, 2018

In this article, the authors comment on the study "Caspr1 is a host receptor for meningitis-causing Escherichia coli" by Zhao et al. (Nat Commun, 2ß18) that identified Caspr1 as a key host receptor for E. coli virulence factor IbeA, facilitating E. coli penetration through the blood-brain barrier (BBB). The research demonstrated that targeting the interaction between IbeA and Caspr1 could potentially neutralize E. coli virulence and prevented meningitis, shedding light on the mechanisms of bacterial invasion into brain endothelial cells and hippocampal neurons.

A global view of substrate phosphorylation and dephosphorylation during budding yeast mitotic exit

July 25, 2018

In this article, the authors comment on the study "Phosphoproteome dynamics during mitotic exit in budding yeast" by Touati (EMBO J, 2018) that described a time-resolved global phosphoproteome analysis during a cell cycle phase known as mitotic exit in budding yeast revealed the principles of phosphoregulation governing the ordered sequence of events such as spindle elongation, chromosome decondensation, and completion of cell division.

Gammaretroviruses tether to mitotic chromatin by directly binding nucleosomal histone proteins

July 24, 2018

In this article, the authors comment on the study "Murine leukemia virus p12 tethers the capsid-containing pre-integration complex to chromatin by binding directly to host nucleosomes in mitosis" by Wanaguruet al. (PLoS Pathog, 2018) that highlights the essential role of the gammaretroviral gag cleavage product, p12, at both early and late stages of the virus life cycle, particularly in the integration of the viral DNA into the host cell chromatin to form a provirus. It also emphasizes the recent findings regarding the N- and C-terminal domains of p12, revealing their direct binding to the viral capsid lattice and nucleosomal histone proteins, respectively, thus elucidating the mechanism by which p12 links the viral pre-integration complex to mitotic chromatin.

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