Vol. 03, 2016
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.
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.
Cryptococcus flips its lid – membrane phospholipid asymmetry modulates antifungal drug resistance and virulence
Erika Shor1, Yina Wang1, David S. Perlin1,2, and Chaoyang Xue1,2
This article comments on work published by Huang et al. (MBio, 2016), which reported that in the pathogenic fungus Cryptococcus neoformans loss of lipid flippase activity sensitized cryptococcal cells to multiple classes of antifungal drugs and abolished fungal virulence in murine models.
A novel component of the mitochondrial genome segregation machinery in trypanosomes
Anneliese Hoffmann1,2, Martin Jakob1, and Torsten Ochsenreiter1
This article comments on work published by Trikin et al. (PLoS Pathog, 2016), which described a new component of the mitochondrial genome segregation machinery in the protozoan parasite Trypanosoma brucei.
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.
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.
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.
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?
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.
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.
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.
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.