Vol. 03, 2016

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

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.

B cell-helping functions of gut microbial metabolites

Chang H. Kim1,2,3,4

This article comments on work published by Kim et al. (Cell Host & Microbe, 2016), which showed that the microbial metabolites short-chain fatty acids (SCFAs) regulate the metabolism and gene expression in B cells to promote antibody production.

How do yeast sense mitochondrial dysfunction?

Dmitry A. Knorre1, Svyatoslav S. Sokolov1, Anna N. Zyrina2, Fedor F. Severin1,3

Apart from energy transformation, mitochondria play important signaling roles. In yeast, mitochondrial signaling relies on several molecular cascades. However, it is not clear how a cell detects a particular mitochondrial malfunction. In our review we argue that in yeast the major known routes of mitochondrial signaling are moderated by non-mitochondrial inputs.

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.

Chlamydia trachomatis Genital Infections

Catherine M. O’Connell and Morgan E. Ferone

Chlamydia trachomatis infections are the most commonly reported sexually transmitted bacterial infections in the US and globally. Ascending infection may result in infertility, ectopic pregnancy and chronic pelvic pain in some women. In this review we provide an overview of current knowledge regarding epidemiology, disease outcomes and effective treatment of chlamydial genital tract infection and explore potential mechanisms facilitating C. trachomatis infection of genital mucosa identified via bioinformatics and other molecular approaches.

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

Joana F Guerreiro1, Belém Sampaio-Marques2,3, Renata Soares4, Ana Varela Coelho4, Cecília Leão2,3, Paula Ludovico2,3, Isabel Sá-Correia1

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

Ryo Higuchi-Sanabria1, Jason D. Vevea1,3, Joseph K. Charalel1,4, Maria L. Sapar5, Liza A. Pon1,2

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

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.

Inhibition of Aβ42 oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs

Sei-Kyoung Park1, Kiira Ratia2, Mariam Ba1, Maria Valencik1 and Susan W. Liebman1,3

The formation of small Aβ42 oligomers has been implicated as a toxic species in Alzheimer disease (AD). Here, we show that the mechanism of the PICALM, human AD risk factor, is likely to reduce the level of Aβ42 oligomers in cells. We screened FDA-approved drugs to identify candidates that prevent the formation of Aβ42 small oligomers using the yeast Aβ42-RF reporter system. We also showed that each of the drug hits counteract yeast and mammalian cell toxicity associated with Aβ42 small aggregates.

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

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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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Construction and evaluation of yeast expression networks by database-guided predictions

May 10, 2016

DNA-Microarrays are powerful tools to obtain expression data on the genome-wide scale. We set out to define a way to cluster microarray data according to their expressional relationship and to obtain information on the significance of this clustering approach.

Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii

May 1, 2016

Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Using an optogenetic sensor to monitor subcellular calcium in this model intracellular pathogen we found a novel regulatory function of phosphatidylthreonine in calcium signaling.

Filamentation protects Candida albicans from amphotericin B-induced programmed cell death via a mechanism involving the yeast metacaspase, MCA1

April 25, 2016

Candida albicans proliferates in two distinct cell types: blastopores and filaments. Programmed cell death is a controlled form of cell suicide that occurs when C. albicans cells are exposed to fungicidal drugs like amphotericin B and caspofungin, and to other stressful conditions. We provide evidence that programmed cell death is cell-type specific in yeast: Filamentous C. albicans cells are more resistant to amphotericin B- and caspofungin-induced programmed cell death than their blastospore counterparts. Our genetic data suggest that this phenomenon is mediated by a protective mechanism involving the yeast metacaspase, MCA1.

A plant Bcl-2-associated athanogene is proteolytically activated to confer fungal resistance

April 16, 2016

This article comments on work published by Li et al. (Plant Cell, 2016), which focuses on the role of Bcl-2-associated athanogene 6 (BAG6) in plant innate immunity, showing that BAG6 plays a key role in basal plant defense against fungal pathogens.

The molecular and cellular action properties of artemisinins: what has yeast told us?

April 14, 2016

Artemisinin (ART) or Qinghaosu is a natural compound possessing superior anti-malarial activity. Although intensive studies have been done in the medicinal chemistry field to understand the structure-effect relationship, the biological actions of artemisinin are poorly understood and controversial. This review summarizes what we have learned from yeast about the basic biological properties of ARTs, as well as some key unanswered questions.

Metabolic network structure and function in bacteria goes beyond conserved enzyme components

April 14, 2016

This article comments on work published by Bazurto et al. (MBio, 2016), which demonstrated that conservation of metabolic components was not sufficient to predict network structure and function Escherichia coli.

Formaldehyde fixation is detrimental to actin cables in glucose-depleted S. cerevisiae cells

April 13, 2016

Actin filaments form cortical patches and emanating cables in fermenting cells of Saccharomyces cerevisiae. We assume that stability of actin cables reflects the metabolic status of the cell. Based on comparison of live and formaldehyde-fixed cells, our data suggest that formaldehyde affects respiration before fixation and this uneven signaling results in destabilization of actin cables in glucose-deprived cells.

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

April 13, 2016

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.

Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe

April 5, 2016

This article comments on work published by Wang et al. (Nat Commun, 2014), which provides insights into the mode-of-action of artemisinin and its specificity against malaria parasites.

Translational repression in malaria sporozoites

April 5, 2016

This article comments on work published by Zhang et al. (PLoS Pathog, 2016), which summarizea recent advances in the translational repression of gene expression in the malaria sporozoite.