Vol. 03, 2016

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.

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

Elizabeth B. Smith, Stephen K. Dolan, David A. Fitzpatrick, Sean Doyle and Gary W. Jones

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

Joana F Guerreiro¹, Belém Sampaio-Marques^2,3, Renata Soares⁴, Ana Varela Coelho⁴, Cecília Leão^2,3, Paula Ludovico^2,3, 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. Vevea^1,3, Joseph K. Charalel^1,4, Maria L. Sapar⁵, Liza A. Pon^1,2

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 Sharma^1,2 and Imtiyaz Yaseen^1,2

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. Liebman^1,3

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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Cryptococcus flips its lid – membrane phospholipid asymmetry modulates antifungal drug resistance and virulence

Erika Shor¹, Yina Wang¹, David S. Perlin^1,2, and Chaoyang Xue^1,2

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.

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.

A novel component of the mitochondrial genome segregation machinery in trypanosomes

Anneliese Hoffmann^1,2, 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.

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. Ruetenik^1,2,3, Alejandro Ocampo^1,2,3,¶, Kai Ruan^4,5,#, Yi Zhu^4,5, Chong Li^4,6, R. Grace Zhai^1,4,5,6 and Antoni Barrientos^1,2,3,5

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.

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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 Bouillaut^1,¶, 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: 2^nd International Symposium on “One Mitochondrion, Many Diseases – Biological and Molecular Perspectives”, a FRIAS Junior Researcher Conference, Freiburg im Breisgau, Germany, March 9^th/10^th, 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 Lays^{1, 2}, Eric Tannier^{2, 3}, Thomas Henry^1,2

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. Kim^1,2,3,4

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. Severin^1,3

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.

Autophagy: one more Nobel Prize for yeast

Andreas Zimmermann¹, Katharina Kainz¹, Aleksandra Andryushkova¹, Sebastian Hofer¹, Frank Madeo^1,2 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. Martin^1,2, 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-Gutierrez^1,*, Katharina Kainz¹ and Frank Madeo^1,2,*

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

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.

Recent Insights into the HIV/AIDS Pandemic

September 4, 2016

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

September 4, 2016

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

August 30, 2016

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

August 25, 2016

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.