Microreviews, Review

The role of transcriptional ‘futile cycles’ in autophagy and microbial pathogenesis

Guowu Hu1, Travis McQuiston1, Amélie Bernard2, Yoon-Dong Park1, Jin Qiu1, Ali Vural3, Nannan Zhang1, Scott R. Waterman1, Nathan H. Blewett4, Timothy G. Myers5, John H. Kehrl3, Gulbu Uzel1, Daniel J. Klionsky2 and Peter R. Williamson1

Eukaryotic cells utilize macroautophagy (hereafter autophagy) to recycle cellular materials during nutrient stress. Target of rapamycin (Tor) is a central regulator of this process, acting by post-translational mechanisms, phosphorylating preformed autophagy-related (Atg) proteins to repress autophagy during log-phase growth. A role for this regulatory process in fungal virulence was further demonstrated by showing that overexpression of the Dcp2-associated mRNA-binding protein Vad1 in the AIDS-associated pathogen Cryptococcus neoformans results in constitutive repression of autophagy even under starvation conditions as well as attenuated virulence in a mouse model. In summary, Tor-dependent post-transcriptional regulation of autophagy plays a key role in the facilitation of microbial pathogenesis.

The many facets of homologous recombination at telomeres

Clémence Claussin and Michael Chang

The ends of linear chromosomes are capped by nucleoprotein structures called telomeres. A dysfunctional telomere may resemble a DNA double-strand break (DSB), which is a severe form of DNA damage. The presence of one DSB is sufficient to drive cell cycle arrest and cell death. Therefore cells have evolved mechanisms to repair DSBs such as homologous recombination (HR). HR-mediated repair of telomeres can lead to genome instability, a hallmark of cancer cells, which is why such repair is normally inhibited. However, some HR-mediated processes are required for proper telomere function. The need for some recombination activities at telomeres but not others necessitates careful and complex regulation, defects in which can lead to catastrophic consequences. Furthermore, some cell types can maintain telomeres via telomerase-independent, recombination-mediated mechanisms. In humans, these mechanisms...

From the baker to the bedside: yeast models of Parkinson’s disease

Regina Menezes1,2, Sandra Tenreiro3,5, Diana Macedo2, Cláudia N. Santos1,2, Tiago Fleming Outeiro4,5,6

The baker’s yeast Saccharomyces cerevisiae has been extensively explored for our understanding of fundamental cell biology processes highly conserved in the eukaryotic kingdom. This review provides a brief historical perspective on the emergence of yeast as an experimental model and on how the field evolved to exploit the potential of the model for tackling the intricacies of various human diseases. In particular, the authors focus on existing yeast models of the molecular underpinnings of Parkinson’s disease (PD), focusing primarily on the central role of protein quality control systems.

Why are essential genes essential? – The essentiality of Saccharomyces genes

Zhaojie Zhang and Qun Ren

Essential genes are defined as required for the survival of an organism or a cell. This article reviews and analyzes the levels of essentiality of the Saccharomyces cerevisiae genes and groups the genes into four categories: (1) Conditional essential: essential only under certain circumstances or growth conditions; (2) Essential: required for survival under optimal growth conditions; (3) Redundant essential: synthetic lethal due to redundant pathways or gene duplication; and (4) Absolute essential: the minimal genes required for maintaining a cellular life under a stress-free environment. The essential and non-essential functions of the essential genes are further analyzed.

Membrane depolarization-triggered responsive diversification leads to antibiotic tolerance

Natalie Verstraeten, Wouter Joris Knapen, Maarten Fauvart, Jan Michiels

In this article, the authors discuss the article "Obg and membrane depolarization are part of a microbial bet-hedging strategy that leads to antibiotic tolerance", Verstraeten et al., Mol. Cell 2015 Jul 2; 59 (1): 9-21.

Evolutionary rewiring of bacterial regulatory networks

Tiffany B. Taylor1,*, Geraldine Mulley1, Liam J. McGuffin1, Louise J. Johnson1, Michael A. Brockhurst2, Tanya Arseneault1,3, Mark W. Silby4 and Robert W. Jackson1,5

Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks – homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. This article discusses Taylor, et al. Science (2015), 347(6225), reporting mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but which come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.

Wanted Plasmodium falciparum, dead or alive

Fatimata Sow1, Mary Nyonda1, Anne-Lise Bienvenu1, 2, Stephane Picot1, 2

In this article, mechanisms of cell death in unicellular parasites are discussed, focussing on “programmed cell death” in Plasmodium.

Yeast as a tool to explore cathepsin D function

H. Pereira1, C.S.F. Oliveira1,2, L. Castro1, A. Preto1, S. R. Chaves1,#, M. Côrte-Real1,#

Cathepsin D has garnered increased attention in recent years, mainly since it has been associated with several human pathologies. This review summarizes how cathepsin D can have both anti- and pro-survival functions depending on its proteolytic activity, cellular context and stress stimulus.

Coordinate responses to alkaline pH stress in budding yeast

Albert Serra-Cardona, David Canadell and Joaquín Ariño

This review summarizes the modulation of a substantial number of signaling pathways whose participate in the alkaline response in yeast. These regulatory inputs involve not only the conserved Rim101/PacC pathway, but also the calcium-activated phosphatase calcineurin, the Wsc1-Pkc1-Slt2 MAP kinase, the Snf1 and PKA kinases and oxidative stress-response pathways.

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New insights in the mode of action of anti-leishmanial drugs by using chemical mutagenesis screens coupled to next-generation sequencing

January 21, 2020

In this article, the authors comment on the study "Coupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania" by Bhattacharya et al. (Nat Commun, 2019), which introduces Mut-seq, a chemical mutagenesis and sequencing approach, to uncover drug resistance mechanisms in Leishmania, revealing links between lipid metabolism genes and miltefosine resistance, and a protein kinase involved in translation conferring paromomycin resistance.

Microfluidic techniques for separation of bacterial cells via taxis

January 15, 2020

Microfluidic tools, ideal for studying microbial motility due to their control over laminar flows at microscopic scales, enable precise analysis of various taxis behaviors and have advanced applications in synthetic biology, directed evolution, and medical microbiology.

Influence of delivery and feeding mode in oral fungi colonization – a systematic review

January 7, 2020

A systematic review of oral fungal colonization in infants found that while breastfeeding did not significantly affect the oral mycobiome, vaginal delivery was associated with higher oral yeast colonization, particularly of Candida albicans.

A holobiont view on thrombosis: unravelling the microbiota’s influence on arterial thrombus growth

January 6, 2020

In this article, the authors comment on the study "The microbiota promotes arterial thrombosis in low-density lipoprotein receptor-deficient mice" by Kiouptsi et al. (mBio, 2019) that showed that commensal microbiota, intricately linked to host physiology, may influence cardiovascular disease, as shown by studies using germ-free atherosclerosis-prone mice to examine how microbial presence and diet affect arterial thrombosis and lesion development.

The role of Lactobacillus species in the control of Candida via biotrophic interactions

November 25, 2019

Microbial communities, including Candida and Lactobacillus species, play a crucial role in human health, particularly in the context of mucosal infections, but our understanding of their interactions and effects is still incomplete due to the variability of species and isolates as well as the complexity of the human host.

Tribal warfare: Commensal Neisseria kill pathogen Neisseria gonorrhoeae using its DNA

October 19, 2019

This article comments on work published by Kim et al (Cell Host Microbe, 2019), which adds a new dimension to the concept of commensal protection. It shows that commensal Neisseria kill the closely related pathogen N. gonorrhoeae through an unexpected mechanism, one that involves genetic competence, DNA methylation state and recombination.

Yet another job for the bacterial ribosome

October 17, 2019

This article comments on work published by Knüpffer et al (mBio, 2019), which revealed the intricate interaction of uL23 with yet another essential player in bacteria, the ATPase SecA, which is best known for its role during post-translational secretion of proteins across the bacterial SecYEG translocon

Gut microbial metabolites in depression: understanding the biochemical mechanisms

September 27, 2019

This article shows how the gut microbiota contributes to the pathophysiology of depression and examines the mechanisms by which microbially-derived molecules may influence depressive behavior, highlighting the potential of dietary interventions as novel therapeutic strategies.

The multiple functions of the numerous Chlamydia trachomatis secreted proteins: the tip of the iceberg

August 21, 2019

CThis article shows an in-depth review on the current knowledge and outstanding questions about secreted proteins from Chlamydia trachomatis, detailing their roles in host cell interaction and immune response evasion.

Inhibiting eukaryotic ribosome biogenesis: Mining new tools for basic research and medical applications

August 20, 2019

This article comments on work published by Awad et al (BMC Biology, 2019), which screened for novel inhibitors of the ribosome biogenesis pathway in yeast.

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