Vol. 03, 2016

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.

Global translational impacts of the loss of the tRNA modification t6A in yeast

Patrick C. Thiaville1,2,3,4, Rachel Legendre4, Diego Rojas-Benítez5, Agnès Baudin-Baillieu4, Isabelle Hatin4, Guilhem Chalancon6, Alvaro Glavic5, Olivier Namy4, Valérie de Crécy-Lagard1,3

The universal tRNA modification t6A is found at position 37 of nearly all tRNAs decoding ANN codons. Analysis of codon occupancy rates suggests that one of the major roles of t6A is to homogenize the process of elongation by slowing the elongation rate at codons decoded by high abundance tRNAs and I34:C3 pairs while increasing the elongation rate of rare tRNAs and G34:U3 pairs. This work reveals that the consequences of t6A absence are complex and multilayered and has set the stage to elucidate the molecular basis of the observed phenotypes.

Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes

Figarella K1, Marsiccobetre S1, Arocha I1, Colina W2, Hasegawa M2,†, Rodriguez M2, Rodriguez-Acosta A3, Duszenko M4, Benaim G5, Uzcategui NL3

The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.

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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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Autophagy: machinery and regulation

Zhangyuan Yin, Clarence Pascual and Daniel J. Klionsky

Macroautophagy/autophagy is an evolutionarily conserved cellular degradation process that targets cytoplasmic materials including cytosol, macromolecules and unwanted organelles. The discovery and analysis of autophagy-related (Atg) proteins have unveiled much of the machinery of autophagosome formation. In this review, we briefly summarize the physiological roles, molecular mechanism, regulatory network, and pathophysiological roles of autophagy.

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.

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.

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.

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.

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.

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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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Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis

June 30, 2016

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

June 27, 2016

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

June 27, 2016

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

June 27, 2016

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?

June 27, 2016

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

June 23, 2016

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.

Antibiotic use in childhood alters the gut microbiota and predisposes to overweight

June 20, 2016

This article comments on work published by Korpela et al. (Nat Commun, 2016), which investigates the correlation between the use of antibiotics in early life and the excessive weight gain in later childhood.

Evidence for the hallmarks of human aging in replicatively aging yeast

June 20, 2016

Recently, efforts have been made to characterize the hallmarks that accompany and contribute to the phenomenon of aging, as most relevant for humans. Remarkably, studying the finite lifespan of the single cell eukaryote budding yeast has been paramount for our understanding of aging. Here, we compile observations from literature over the past decades of research on replicatively aging yeast to highlight how the hallmarks of aging in humans are present in yeast.

Increased spontaneous recombination in RNase H2-deficient cells arises from multiple contiguous rNMPs and not from single rNMP residues incorporated by DNA polymerase epsilon

May 15, 2016

Ribonucleotides (rNMPs) can become embedded in DNA from insertion by DNA polymerases, failure to remove Okazaki fragment primers, R-loops that can prime replication, and RNA/cDNA-mediated recombination. We report here that recombination is not stimulated by rNMPs incorporated by the replicative polymerase epsilon. Instead, recombination seems to be stimulated by multiple contiguous rNMPs, which may arise from R-loops or replication priming events.

Bacterial outer membrane vesicle biogenesis: a new mechanism and its implications

May 10, 2016

This article comments on work published by Roier et al. (Nat Commun, 2016), which proposes a novel and highly conserved bacterial outer membane vesicle biogenesis mechanism based on phospholipid accumulation in the outer leaflet of the outer membrane.