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
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.
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.
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.
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.
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.
Inhibition of Zika virus by Wolbachia in Aedes aegypti
Eric Pearce Caragata, Heverton Leandro Carneiro Dutra and Luciano Andrade Moreira
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
Lola V. Stamm
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.
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.
Inhibition of Aβ42 oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs
January 18, 2016
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
December 31, 2015
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
December 31, 2015
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
December 25, 2015
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
December 18, 2015
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
December 11, 2015
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.
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.