Vol. 03, 2016

Bacterial genotoxin functions as immune-modulator and promotes host survival

R. Guidi1, L. Del Bell Belluz2, T. Frisan2

This article comments on work published by Del Bel Belluz et al. (PLoS Pathog, 2016), which demonstrated that the typhoid toxin of Salmonella enterica serovar Typhi esembles an immune-modulatory molecule rather than a toxic agent.

Functions and regulation of the MRX complex at DNA double-strand breaks

Elisa Gobbini1, Corinne Cassani1, Matteo Villa1, Diego Bonetti2 and Maria Pia Longhese1

DNA double-strand breaks (DSBs) pose a serious threat to genome stability and cell survival. Cells possess mechanisms that recognize DSBs and promote their repair through either homologous recombination (HR) or non-homologous end joining (NHEJ). The present review focuses mainly on recent works in the budding yeast Saccharomyces cerevisiae to highlight structure and regulation of the evolutionary conserved Mre11-Rad50-Xrs2 (MRX) complex as well as its interplays with Tel1.

Attenuation of polyglutamine-induced toxicity by enhancement of mitochondrial OXPHOS in yeast and fly models of aging

Andrea L. Ruetenik1,2,3, Alejandro Ocampo1,2,3,¶, Kai Ruan4,5,#, Yi Zhu4,5, Chong Li4,6, R. Grace Zhai1,4,5,6 and Antoni Barrientos1,2,3,5

Defects in mitochondrial biogenesis and function are common in many neurodegenerative disorders, including Huntington’s disease (HD). We could shown that enhancement of mitochondrial biogenesis protects against neurodegeneration in HD yeast and fly models. Our results suggest that therapeutic interventions aiming at the enhancement of mitochondrial respiration and OXPHOS could reduce polyQ toxicity and delay disease onset.

Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

Richard Dela Cruz1,2, Mi-Young Jeong1 and Dennis R. Winge1

Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. In this report, we describe the isolation of a robust suppressor of the respiratory defect in cox23∆ cells that mapped to the mitochondrial-encoded Cox1 subunit.

Inhibition of Zika virus by Wolbachia in Aedes aegypti

Eric Pearce Caragata, Heverton Leandro Carneiro Dutra and Luciano Andrade Moreira

This article comments on work published by Dutra et al. (Cell Host Microbe, 2016), which investigated the potential of Wolbachia infections in Aedes aegypti to restrict infection and transmission of Zika virus.

Syphilis: Re-emergence of an old foe

Lola V. Stamm

Syphilis is caused by infection with Treponema pallidum subsp. pallidum, a not-yet-cultivable spiral-shaped bacterium that is usually transmitted by sexual contact with an infected partner or by an infected pregnant woman to her fetus. This review provides insights into the etiology, epidemiology, clinical manifestation, diagnosis, treatment and prevention of syphilis.

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

Dinesh Jaishankar1,2,4 and Deepak Shukla1,2,3

Genital herpes is one of the most common, persistent and highly infectious sexually transmitted viral infections. This review provides an insight into the epidemiology, pathology, our current understanding of the molecular mechanisms of infection and the currently available and upcoming treatments for genital herpes.

Trichomoniasis – are we giving the deserved attention to the most common non-viral sexually transmitted disease worldwide?

Camila Braz Menezes, Amanda Piccoli Frasson, Tiana Tasca

Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease (STD) in the world. This article contributes to claim the attention of public health policies to control this STD.

House of cellulose – a new hideout for drug tolerant Mycobacterium tuberculosis

Ashwani Kumar

This article comments on work published by Trivedi et al. (Nat Commun, 2016), which shows that Mycobacterium tuberculosis cells organise themselves into biofilms in response to intracellular thiol reductive stress.

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NprR, a moonlighting quorum sensor shifting from a phosphatase activity to a transcriptional activator

Stéphane Perchat1, Antoine Talagas2, Samira Zouhir2, Sandrine Poncet1, Laurent Bouillaut1,¶, Sylvie Nessler2 and Didier Lereclus1

This article comments on work published by Perchat et al. (PLoS Pathog, 2016), which demonstrates that, in the absence of the signaling peptide NprX, the sensor NprR is a dimer, which negatively controls sporulation in Bacillus thuringiensis, independently of its transcription factor activity.

The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription

Rubin Jiao1, Liubov Lobanova1, Amanda Waldner1, Anthony Fu1, Linda Xiao1, Troy A. Harkness1, and Terra G. Arnason1,2

The SNF1 kinase class of serine/threonine kinases, which includes the AMP-dependent protein kinase (AMPK) in other systems, are of widespread interest because of their important roles in glucose homeostasis, stress resistance, and aging. Our goal was to identify discrete ubiquitin-conjugating enzymes that are involved in SNF1 kinase activity in response to glucose levels and anticipated revealing those which are involved in Snf1-Ub attachment. Here, we report that the cell cycle and stress-related E2, Ubc1, indirectly affects SNF1 kinase activity not through stability, but through upstream events.

Threading Granules in Freiburg: 2nd International Symposium on “One Mitochondrion, Many Diseases – Biological and Molecular Perspectives”, a FRIAS Junior Researcher Conference, Freiburg im Breisgau, Germany, March 9th/10th, 2016

Ralf J. Braun1, Ralf M. Zerbes2, Florian Steinberg3, Denis Gris4, and Verónica I. Dumit5

INTRODUCTION Mitochondria (greek: μίτος & χονδρίον, mitos & chondrion, i.e., thread & granule) are the power houses of eukaryotic cells, and are pivotally involved in essential metabolic processes, including iron/sulfur

The interaction between herpes simplex virus 1 genome and promyelocytic leukemia nuclear bodies (PML-NBs) as a hallmark of the entry in latency

Patrick Lomonte

This article comments on work published by Maroul et al. (PLoS Pathog, 2016), which demonstrates that the interaction of the viral genomes with the nuclear architecture and specifically the promyelocytic leukemia nuclear bodies is a major determinant for the entry of HSV-1 into latency.

Francisella IglG protein and the DUF4280 proteins: PAAR-like proteins in non-canonical Type VI secretion systems?

Claire Lays1, 2, Eric Tannier2, 3, Thomas Henry1,2

This article comments on work published by Rigard et al. (PLoS Pathog, 2013), which identified the function of IgIG, a protein of unknown function, encoded within the Francisella Pathogenicity Island.

Sulfur transfer and activation by ubiquitin-like modifier system Uba4•Urm1 link protein urmylation and tRNA thiolation in yeast

André Jüdes1, Alexander Bruch1, Roland Klassen1, Mark Helm2 and Raffael Schaffrath1

Urm1 is a unique dual-function member of the ubiquitin protein family and conserved from yeast to man. It acts both as a protein modifier in ubiquitin-like urmylation and as a sulfur donor for tRNA thiolation. We therefore studied whether Urm1 dual-functions may be interlinked by comparing both tRNA thiolation and urmylation under URM1 pathway inactivating conditions. We found that the two URM1 pathway branches, tRNA thiolation and protein urmylation, are chemically linked through sulfur supply, transfer and activation by the ubiquitin-like modifier system Uba4•Urm1

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Mek1/Mre4 is a master regulator of meiotic recombination in budding yeast

Nancy M. Hollingsworth

This article comments on work published by Chen et al. (PLoS BIol, 2015), showing that the meiosis specific kinase Mek1 indirectly regulates the crossover/non-crossover decision between homologs as well as genetic interference and suggests Mek1 to be a "master regulator" of meiotic recombination in budding yeast.

Shaping meiotic chromosomes with SUMO: a feedback loop controls the assembly of the synaptonemal complex in budding yeast

Hideo Tsubouchi1, Bilge Argunhan1 and Tomomi Tsubouchi2

This article comments on work published by Leung et al. (J Cell Biol, 2015), which shows that the formation of the meiosis-specific synaptonemal complex is controlled through SUMOylation of a regulator required for the assembly of transverse filaments, implicating the involvement of a positive feedback loop in the control of synaptonemal complex assembly.

Learning epigenetic regulation from mycobacteria

Sanjeev Khosla1, Garima Sharma1,2 and Imtiyaz Yaseen1,2

This article comments on work published by Koshla et al. (Nat Commun, 2015), which shows that pathogenic Mycobacterium tuberculosis has evolved strategies to hijack the epigenetic regulation of host transcripton for its own survival.

Location, location, location. Salmonella senses ethanolamine to gauge distinct host environments and coordinate gene expression

Christopher J. Anderson and Melissa M. Kendall

This article comments on work published by Anderson and Kendell (PLoS Pathog, 2015), which demonstrates that Salmonella enterica serovar Typhimurium (Salmonella) exploits ethanolamine signaling to adapt to distinct host environments to precisely coordinate expression of genes encoding metabolism and virulence.

Biofilm assembly becomes crystal clear – filamentous bacteriophage organize the Pseudomonas aeruginosa biofilm matrix into a liquid crystal

Patrick R. Secor1, Laura K. Jennings1, Lia A. Michaels1, Johanna M. Sweere2, Pradeep K. Singh1, William C. Parks3, Paul L. Bollyky2

This article comments on work published by Secor et al. (Host Cell & Microbe, 2015), which highlights a previously unknown role for filamentous Pf phage in organizing the P. aeruginosa biofilm matrix into a liquid crystalline structure. These findings help ground our understanding of biofilm formation within established paradigms of soft matter physics

Histone modifications as regulators of life and death in Saccharomyces cerevisiae

Birthe Fahrenkrog

The mechanism by which chromosomes restructure during apoptosis is still poorly understood, but it is becoming increasingly clear that altered epigenetic histone modifications are fundamental parameters that influence the chromatin state and the nuclear rearrangements within apoptotic cells. This review highlights recent work on the epigenetic regulation of programmed cell death in budding yeast.

Spermidine cures yeast of prions

Shaun H. Speldewinde, and Chris M. Grant

This article comments on work published by Speldewinde and Grant (Mol Biol Cell, 2015), which found that spermidine, a polyamine that has been used to increase autophagic flux, acts as a protective agent which prevents spontaneous prion formation in yeast.

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Autophagy: one more Nobel Prize for yeast

Andreas Zimmermann1, Katharina Kainz1, Aleksandra Andryushkova1, Sebastian Hofer1, Frank Madeo1,2 and Didac Carmona-Gutierrez1

The recent announcement of the 2016 Nobel Prize in Physiology or Medicine, awarded to Yoshinori Ohsumifor the discoveries of mechanisms governing autophagy, underscores the importance of intracellular degradation and recycling. Here we provide a quick historical overview that mirrors both the importance of autophagy as a conserved and essential process for cellular life and death as well as the crucial role of yeast in its mechanistic characterization.

Physiology, phylogeny, and LUCA

William F. Martin1,2, Madeline C. Weiss1, Sinje Neukirchen3, Shijulal Nelson-Sathi4, Filipa L. Sousa3

Genomes record their own history. But if we want to look all the way back to life's beginnings some 4 billion years ago, the record of microbial evolution that is preserved in prokaryotic genomes is not easy to read. The classical approach has been to look for genes that are universally distributed. Another approach is to make all trees for all genes, and sift out the trees where signals have been overwritten by lateral gene transfer. What is left ought to be ancient. If we do that, what do we find?

The curious case of vanishing mitochondria

Anna Karnkowska1 and Vladimír Hampl2

Due to their involvement in the energy metabolism, mitochondria are essential for most eukaryotic cells. Microbial eukaryotes living in low oxygen environments possess reduced forms of mitochondria, namely mitochondrion-related organelles (MROs). Recently, the first microbial eukaryote with neither mitochondrion nor MRO was characterized – Monocercomonoides sp. The discovery of such bona fide amitochondriate eukaryote broadens our knowledge about the diversity and plasticity of eukaryotic cells and provides a substantial contribution to our understanding of eukaryotic cell evolution.

Accumulation of metabolic side products might favor the production of ethanol in Pho13 knockout strains

Guido T. Bommer, Francesca Baldin & Emile Van Schaftingen

This article comments on work published by Collard et al. (Nat Chem Biol, 2016), which describes the discovery of a striking example illustrating the metabolite repair concept.

Sexually transmitted infections: old foes on the rise

Didac Carmona-Gutierrez1,*, Katharina Kainz1 and Frank Madeo1,2,*

Sexually transmitted infections (STIs) are commonly spread via sexual contact. It is estimated that one million STIs are acquired every day worldwide. Besides their impact on sexual, reproductive and neonatal health, they can cause disastrous and life-threatening complications if left untreated. In addition to this personal burden, STIs also represent a socioeconomic problem, deriving in treatment costs of tremendous proportions. Despite a substantial progress in diagnosis, treatment and prevention, the incidence of many common STIs is increasing, and STIs continue to represent a global public health problem and a major cause for morbidity and mortality. With this Special Issue, Microbial Cell provides an in-depth overview of the eight major STIs, covering all relevant features of each infection.

Similar environments but diverse fates: Responses of budding yeast to nutrient deprivation.

Saul M. Honigberg

Diploid budding yeast (Saccharomyces cerevisiae) can adopt one of several alternative differentiation fates in response to nutrient limitation, and each of these fates provides distinct biological functions. When different strain backgrounds are taken into account, these various fates occur in response to similar environmental cues, are regulated by the same signal transduction pathways, and share many of the same master regulators. I propose that the relationships between fate choice, environmental cues and signaling pathways are not Boolean, but involve graded levels of signals, pathway activation and master-regulator activity.

Non-genetic impact factors on chronological lifespan and stress resistance of baker’s yeast

Michael Sauer and Diethard Mattanovich

This article comments on work published by Bisschops et al. (Microbial Cell, 2015), which illustrates how important the choice of the experimental setup is and how culture conditions influcence cellular aging and survival in biotechnological processes.

The complexities of bacterial-fungal interactions in the mammalian gastrointestinal tract

Eduardo Lopez-Medina1 and Andrew Y. Koh2

This article comments on work published by Lopez-Medina et al. (PLoS Pathog, 2015) and Fan et al. (Nat Med, 2015), which utilize an “artificial” niche, the antibiotic-treated gut with concomitant pathogenic microbe expansion, to gain insight in bacterial-fungal interactions in clinically common scenarios.

Gearing up for survival – HSP-containing granules accumulate in quiescent cells and promote survival

Ruofan Yu and Weiwei Dang

This article comments on work published by Lee et al. (Microbial Cell, 2016), which reports that distinct granules are formed in quiescent and non-quiescent cells, which determines their respective cell fates.

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Yeast screening platform identifies FDA-approved drugs that reduce Aβ oligomerization

March 3, 2016

This article comments on work published by Park et al. (Microbial Cell, 2016), which discovered a number of small molecules capable of modulating Aβ aggregation in a yeast model.

Differentiated cytoplasmic granule formation in quiescent and non-quiescent cells upon chronological aging

March 3, 2016

Stationary phase cultures represent a complicated cell population comprising at least two different cell types, quiescent (Q) and non-quiescent (NQ) cells. The authors show that the cell fate of NQ cells is largely irreversible even if they are allowed to reenter mitosis. Their results reveal that the formation of different granule structures may represent the early stage of cell type differentiation in yeast stationary phase cultures.

Mitochondrial regulation of cell death: a phylogenetically conserved control

February 23, 2016

Mitochondria are fundamental for eukaryotic cells as they participate in critical catabolic and anabolic pathways. Moreover, mitochondria play a key role in the signal transduction cascades that precipitate many (but not all) regulated variants of cellular demise. In this short review, the authors discuss the differential implication of mitochondria in the major forms of regulated cell death.

Mek1/Mre4 is a master regulator of meiotic recombination in budding yeast

February 22, 2016

This article comments on work published by Chen et al. (PLoS BIol, 2015), showing that the meiosis specific kinase Mek1 indirectly regulates the crossover/non-crossover decision between homologs as well as genetic interference and suggests Mek1 to be a "master regulator" of meiotic recombination in budding yeast.

Shaping meiotic chromosomes with SUMO: a feedback loop controls the assembly of the synaptonemal complex in budding yeast

February 19, 2016

This article comments on work published by Leung et al. (J Cell Biol, 2015), which shows that the formation of the meiosis-specific synaptonemal complex is controlled through SUMOylation of a regulator required for the assembly of transverse filaments, implicating the involvement of a positive feedback loop in the control of synaptonemal complex assembly.

Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity

February 19, 2016

Gliotoxin is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus. In order to produce gliotoxin the host organism needs to have evolved a self-protection mechanism. The authors demonstrate that the activity of a novel thiomethyltransferase is requiered for protection against exogenous gliotoxin and provide implications for understanding the evolution of gliotoxin self-protection mechanisms.

Mitochondrial proteomics of the acetic acid – induced programmed cell death response in a highly tolerant Zygosaccharomyces bailii – derived hybrid strain

January 22, 2016

Very high concentrations of acetic acid at low pH induce programmed cell death (PCD) in both the experimental model Saccharomyces cerevisiae and in Zygosaccharomyces bailii, the latter being considered the most problematic acidic food spoilage yeast due to its remarkable intrinsic resistance to this food preservative. This study offers insights into the mechanisms involved in acetic acid - induced PCD in the Z. bailii-derived hybrid strain ISA1307 by analyzing the yeast mitochondrial protein expression profile of cells challenged by acetic acid.

The transcriptional repressor Sum1p counteracts Sir2p in regulation of the actin cytoskeleton, mitochondrial quality control and replicative lifespan in Saccharomyces cerevisiae

January 18, 2016

Increasing the stability or dynamics of the actin cytoskeleton can extend lifespan in C. elegans and S. cerevisiae. Actin cables of budding yeast, bundles of actin filaments that mediate cargo transport, affect lifespan control through effects on mitochondrial quality control. Here, we report that Sum1p and Sir2p inversely regulate actin and mitochondrial maintenance, as well as lifespan.

Learning epigenetic regulation from mycobacteria

January 18, 2016

This article comments on work published by Koshla et al. (Nat Commun, 2015), which shows that pathogenic Mycobacterium tuberculosis has evolved strategies to hijack the epigenetic regulation of host transcripton for its own survival.

Location, location, location. Salmonella senses ethanolamine to gauge distinct host environments and coordinate gene expression

January 18, 2016

This article comments on work published by Anderson and Kendell (PLoS Pathog, 2015), which demonstrates that Salmonella enterica serovar Typhimurium (Salmonella) exploits ethanolamine signaling to adapt to distinct host environments to precisely coordinate expression of genes encoding metabolism and virulence.

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