Vol. 03, 2016

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

Jannell V. Bazurto# and Diana M. Downs

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

Pavla Vasicova1,#, Mark Rinnerthaler2, Danusa Haskova1, Lenka Novakova1, Ivana Malcova1, Michael Breitenbach2, Jiri Hasek1

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

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.

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

Jigang Wang1,2,# and Qingsong Lin2

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

Oliver Turque1, Tiffany Tsao1, Thomas Li1 and Min Zhang1,2

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.

Chromatin binding and silencing: Two roles of the same protein Lem2

Ramón Ramos Barrales and Sigurd Braun

This article comments on work published by Barrales et al. (Genes Dev, 2016), which identifies the nuclear envelope protein Lem2, a homolog of metazoan lamin-associated proteins (LAPs), as a relevant factor for heterochromatin silencing and perinuclear localization in the fission yeast Schizosaccharomyces pombe.

When and where? Pathogenic Escherichia coli differentially sense host D-serine using a universal transporter system to monitor their environment

James P. R. Connolly and Andrew J. Roe

This article comments on work published by Connolly et al. (PLoS Pathog, 2016), which describes the discovery of a functional and previously uncharacterized D-serine uptake system in E. coli.

Signaling pathways and posttranslational modifications of tau in Alzheimer’s disease: the humanization of yeast cells

Jürgen J. Heinisch1 and Roland Brandt2

In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. Substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. We give an overview on common modifications as they occur in tau during AD and discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells.

Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1

Laila Moustaq, Iwona I. Smaczynska-de Rooij, Sarah E. Palmer, Christopher J. Marklew, Kathryn R. Ayscough

The dynamins represent a superfamily of proteins that have been shown to function in a wide range of membrane fusion and fission events. An increasing number of mutations in the human classical dynamins, Dyn-1 and Dyn-2 has been reported, with diseases caused by these changes ranging from Charcot-Marie-Tooth disorder to epileptic encephalopathies. This study aimed to use the dynamin-like protein Vps1 of Saccharomyces cerevisiae as a model to gain insights into the mechanistic defects caused by specific dynamin mutations considered to underlie a number of diseases.

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HPV disease transmission protection and control

Neil D. Christensen

Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. In this review we present an overview of papillomavirus biology and propose a series of questions that provide a basis for discussion of some areas of interest that continue to represent important gaps in our knowledge in the HPV research field.

Hepatitis B virus and its sexually transmitted infection – an update

Takako Inoue1 and Yasuhito Tanaka1,2

About 5% of the world’s population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The purpose of this article is to provide up-to-date information on HBV and HBV infection as a major sexually transmitted infection.

Recent Insights into the HIV/AIDS Pandemic

Juan C. Becerra1, Lukas S. Bildstein2, Johannes S. Gach1

Acquired immunodeficiency syndrome (AIDS), caused by chronic infection with the human immunodeficiency virus1 (HIV-1), is one of the most devastating pandemics ever recorded in human history. In this review, we assemble new details on the molecular events from the attachment of the virus, to the assembly and release of the viral progeny.

Gonorrhea – an evolving disease of the new millennium

Stuart A. Hill, Thao L. Masters and Jenny Wachter

Neisseria gonorrhoeae (the gonococcus) is a Gram-negative diplococcus, an obligate human pathogen, and the etiologic agent of the sexually transmitted disease, gonorrhea. This review provides insight into the molecular epidemiology, virulence mechanisms, pathogenesis and therapeutic options.

Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets

January Weiner 3rd1 and Taco W.A. Kooij2

In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites.

VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast

Dário Trindade1,2, Clara Pereira3,4, Susana R. Chaves1, Stéphen Manon2, Manuela Côrte-Real1 and Maria João Sousa1

Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. In this study, we sought to determine whether Por1p functionally interacts with ADP/ATP carrier (AAC) proteins, as well as its contribution to cytochrome c release and yeast apoptosis induced by acetic acid treatment. Our data indicate that Por1p may regulate cell survival by acting as a negative regulator of AAC proteins in the apoptotic cascade.

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

Jigang Wang1,2,# and Qingsong Lin2

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

Oliver Turque1, Tiffany Tsao1, Thomas Li1 and Min Zhang1,2

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.

Chromatin binding and silencing: Two roles of the same protein Lem2

Ramón Ramos Barrales and Sigurd Braun

This article comments on work published by Barrales et al. (Genes Dev, 2016), which identifies the nuclear envelope protein Lem2, a homolog of metazoan lamin-associated proteins (LAPs), as a relevant factor for heterochromatin silencing and perinuclear localization in the fission yeast Schizosaccharomyces pombe.

When and where? Pathogenic Escherichia coli differentially sense host D-serine using a universal transporter system to monitor their environment

James P. R. Connolly and Andrew J. Roe

This article comments on work published by Connolly et al. (PLoS Pathog, 2016), which describes the discovery of a functional and previously uncharacterized D-serine uptake system in E. coli.

Signaling pathways and posttranslational modifications of tau in Alzheimer’s disease: the humanization of yeast cells

Jürgen J. Heinisch1 and Roland Brandt2

In the past decade, yeast have been frequently employed to study the molecular mechanisms of human neurodegenerative diseases, generally by means of heterologous expression of genes encoding the relevant hallmark proteins. Substantial posttranslational modifications of many of these proteins are required for the development and progression of potentially disease relevant changes. We give an overview on common modifications as they occur in tau during AD and discuss potential approaches to humanize yeast in order to create modification patterns resembling the situation in mammalian cells.

The bacterial cell cycle checkpoint protein Obg and its role in programmed cell death

Liselot Dewachter1, Natalie Verstraeten1, Maarten Fauvart1,2 and Jan Michiels1

This article comments on work published by Dewachter et al. (mBio, 2015), which identified a programmed cell death mechanism in Escherichia coli that is triggered by a mutant isoform of the essential GTPase ObgE.

Bactericidal antibiotics induce programmed metabolic toxicity

Aislinn D. Rowan, Damien J. Cabral and Peter Belenky

This article comments on work published by Lobritz et al. (PNAS, 2015), which demonstrates that bactericidal antibiotics induce metabolic perturbations that are linked to and required for bactericidal antibiotic toxicity.

Control of the gut microbiome by fecal microRNA

Shirong Liu and Howard L. Weiner

This article comments on work published by Liu et al. (Cell Host & Microbe, 2016), which identifies miRNAs in gut lumen and feces of both mice and humans that were able to enter bacteria, specifically regulate bacterial gene transcripts and affect bacterial growth thereby regulating the gut microbiome.

Mitochondrial regulation of cell death: a phylogenetically conserved control

Lorenzo Galluzzi1,2,3,4,5, Oliver Kepp1,2,3,4,6 and Guido Kroemer1,2,3,4,6,7,8

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.

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

October 30, 2016

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

October 24, 2016

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

September 30, 2016

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

September 23, 2016

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

September 23, 2016

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?

September 22, 2016

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

September 4, 2016

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

September 4, 2016

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.

HPV disease transmission protection and control

September 4, 2016

Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. In this review we present an overview of papillomavirus biology and propose a series of questions that provide a basis for discussion of some areas of interest that continue to represent important gaps in our knowledge in the HPV research field.

Hepatitis B virus and its sexually transmitted infection – an update

September 4, 2016

About 5% of the world’s population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The purpose of this article is to provide up-to-date information on HBV and HBV infection as a major sexually transmitted infection.

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