Vol. 02, 2015

EzrA: a spectrin-like scaffold in the bacterial cell division machinery

Robert M Cleverley, Richard J Lewis

Much progress has been made in identifying the components of the divisome, the assembly of proteins that undertakes the vital process of cell division in bacteria. However, how the highly interdependent processes on either side of the membrane are coordinated during division is a major unresolved question. This comment discusses the article "Structure and function of a spectrin-like regulator of bacterial cytokinesis" by Cleverley et al. (2014), Nat Commun.

Microbial hara-kiri: Exploiting lysosomal cell death in malaria parasites

Jun-Hong Ch’ng^1,2, Johan Ursing² and Kevin Shyong-Wei Tan¹

The antimalarial drug chloroquine (CQ) has been sidelined in the fight against falciparum malaria due to wide-spread CQ resistance. This comment discusses the article "Validation of a chloroquine-induced cell death mechanism for clinical use against malaria" by Ch'ng et al. (2014), Cell Death Dis.

Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites

Carine F. Djuika¹, Jaime Huerta-Cepas², Jude M. Przyborski³, Sophia Deil¹, Cecilia P. Sanchez¹, Tobias Doerks², Peer Bork², Michael Lanzer¹ and Marcel Deponte¹

Horizontal gene transfer has emerged as a crucial driving force for the evolution of eukaryotes. This also includes Plasmodium falciparum and related economically and clinically relevant apicomplexan parasites, whose rather small genomes have been shaped not only by natural selection in different host populations but also by horizontal gene transfer following endosymbiosis. However, there is rather little reliable data on horizontal gene transfer between animal hosts or bacteria and apicomplexan parasites. Here we show that apicomplexan homologues of peroxiredoxin 5 (Prx5) have a prokaryotic ancestry and therefore represent a special subclass of Prx5 isoforms in eukaryotes. Using two different immunobiochemical approaches, we found that...

The emerging role of complex modifications of tRNA^Lys_UUU in signaling pathways

Patrick C. Thiaville^1,2,3,4 and Valérie de Crécy-Lagard^2,4

This comment discusses the article "Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling" by Scheidt et al (Microbial Cell, 2014).

Two distinct and competitive pathways confer the cellcidal actions of artemisinins

Chen Sun^#, Jian Li^#, Yu Cao, Gongbo Long and Bing Zhou

The biological actions of artemisinin (ART), an antimalarial drug derived from Artemisia annua, remain poorly understood and controversial. This article concludes that ARTs are endowed with two major and distinct types of properties: a potent and specific mitochondria-dependent reaction and a more general and less specific heme-mediated reaction. The competitive nature of these two actions could be explained by their shared source of the consumable ARTs, so that inhibition of the heme-mediated degradation pathway would enable more ARTs to be available for the mitochondrial action. These properties of ARTs can be used to interpret the divergent antimalarial and anticancer actions of ARTs.

A pseudokinase couples signaling pathways to enable asymmetric cell division in a bacterium

W. Seth Childers and Lucy Shapiro

In this article, the authors comment on the study "Cell fate regulation governed by a repurposed bacterial histidine kinase" by Childers et al., PLoS Biol. 2014 Oct 28;12(10):e1001979.

Targeting of chromatin readers: a novel strategy used by the Shigella flexneri virulence effector OspF to reprogram transcription

Habiba Harouz, Christophe Rachez, Benoit Meijer, Christian Muchardt, Laurence Arbibe.

In this microreview, the authors discuss the article "Shigella flexneri targets the HP1γ subcode through the phosphothreoninelyase OspF" by Harouz et al. (2014), EMBO J, 22 : 2606-2622.

Intracellular phase for an extracellular bacterial pathogen: MgtC shows the way

Audrey Bernut^1,#, Claudine Belon¹, Chantal Soscia², Sophie Bleves², Anne-Béatrice Blanc-Potard¹

This article discusses the article "A macrophage subversion factor is shared by intracellular and extracellular pathogens" by Belon et al. (PLoS Pathogens 11(6): e1004969, 2015).

Subverting lysosomal function in Trypanosoma brucei

Sam Alsford

This article discusses Koh et al. (2015) "The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei (Microbial Cell 2(8): 288-298).

A single mutation in the 15S rRNA gene confers non sense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria

Ali Gargouri, Catherine Macadré and Jaga Lazowska

This article presents the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. A hypothetical mechanism of suppression by "ribosome shifting" is also discussed in view of the nature of mutations suppressed and not suppressed.

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...

The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei

Hazel Xinyu Koh^1,2, Htay Mon Aye¹, Kevin S. W. Tan² and Cynthia Y. He¹

Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization. We measured drug concentrations that inhibit cell proliferation by 50% (IC50) for several compounds, chosen based on their lysosomotropic effects previously reported in Plasmodium falciparum. The lysosomal effects and cell death induced by L-leucyl-L-leucyl methyl ester (LeuLeu-OMe) were further analyzed by flow cytometry and immunofluorescence analyses of different lysosomal markers...

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Mitochondrial type II NAD(P)H dehydrogenases in fungal cell death

Pedro Gonçalves^1,2,4, Arnaldo Videira^1,2,3

During aerobic respiration, cells produce energy through oxidative phosphorylation, which includes a specialized group of multi-subunit complexes in the inner mitochondrial membrane known as the electron transport chain. However, this canonical pathway is branched into single polypeptide alternative routes in some fungi, plants, protists and bacteria. They confer metabolic plasticity, allowing cells to adapt to different environmental conditions and stresses...

EzrA: a spectrin-like scaffold in the bacterial cell division machinery

Robert M Cleverley, Richard J Lewis

Microbial hara-kiri: Exploiting lysosomal cell death in malaria parasites

Jun-Hong Ch’ng^1,2, Johan Ursing² and Kevin Shyong-Wei Tan¹

A pseudokinase couples signaling pathways to enable asymmetric cell division in a bacterium

W. Seth Childers and Lucy Shapiro

In this article, the authors comment on the study "Cell fate regulation governed by a repurposed bacterial histidine kinase" by Childers et al., PLoS Biol. 2014 Oct 28;12(10):e1001979.

Targeting of chromatin readers: a novel strategy used by the Shigella flexneri virulence effector OspF to reprogram transcription

Habiba Harouz, Christophe Rachez, Benoit Meijer, Christian Muchardt, Laurence Arbibe.

In this microreview, the authors discuss the article "Shigella flexneri targets the HP1γ subcode through the phosphothreoninelyase OspF" by Harouz et al. (2014), EMBO J, 22 : 2606-2622.

Groupthink: chromosomal clustering during transcriptional memory

Kevin A. Morano

In this article, the authors comment on the study "NO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering." by Brickner et al. (Microbial Cell, 2015), discussing the importance and molecular mechanisms of chromosomal clustering during transcriptional memory.

Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration

Amit Shrestha^{1, 2} and Lynn A. Megeney^{1, 2, 3}

Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. This article discusses the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease.

Starting with a degron: N-terminal formyl-methionine of nascent bacterial proteins contributes to their proteolytic control

R. Jürgen Dohmen

In this article, the author comments on the study "Formyl-methionine as a degradation signal at the N-termini of bacterial proteins." by Piatkov et al. (Microbial Cell, 2015), discussing a novel N-terminal degradation signal (N-degron) that targets nascent proteins for degradation in Escherichia coli by a new branch of the bacterial N-end rule pathway, termed the fMet/N-end rule pathway

Elongation factor-P at the crossroads of the host-endosymbiont interface

Andrei Rajkovic¹, Anne Witzky², William Navarre³, Andrew J. Darwin⁴ and Michael Ibba⁵

Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. Here, the authors highlight the recent discoveries made regarding EPMSs, with a focus on how these incomplete modification pathways shape or have been shaped by the endosymbiont-host relationship.

Feelin’ it: Differential oxidative stress sensing mediated by Cyclin C

W. Scott Moye-Rowley

Microbial cells that live exposed directly to their environmental milieu are faced with the challenge of adapting to the dynamic stress conditions that will inevitably be encountered. These stress conditions may vary over wide ranges and the most efficient responses would be tuned to produce a proportional buffering change. A mild stress would most efficiently be dealt with by a mild metabolic reprogramming that would prevent serious damage. A more severe environmental challenge would demand a more dramatic cellular compensatory response.

Subverting lysosomal function in Trypanosoma brucei

Sam Alsford

Toxoplasma control of host apoptosis: the art of not biting too hard the hand that feeds you

Sébastien Besteiro

Toxoplasma gondii is an obligate intracellular parasite that is able to infect a multitude of different vertebrate hosts and can survive in virtually any nucleated cell. Here, the authors discuss the article "Toxoplasma gondii inhibits cytochrome c-induced caspase activation in its host cell by interference with holo-apoptosome assembly" by Graumann et al. (2015, Microbial Cell).

A safety catch for ornithine decarboxylase degradation

Christof Taxis

Feedback inhibition is a common mechanism to adjust the activity of an enzyme in accordance with the abundance of a product. This article comments on the study "Polyamines directly promote antizyme-mediated degradation of ornithine decarboxylase by the proteasome" by Beenukumar et al. (2015), Microbial Cell.

Fancy a gene? A surprisingly complex evolutionary history of peroxiredoxins.

Alena Zíková^1,2, Miroslav Oborník^1,2,3 and Julius Lukeš^1,2,4

In this comment, the authors discuss the article "Prokaryotic ancestry and gene fusion of a dual localized peroxiredoxin in malaria parasites" (Djuika et al., Microbial Cell 2015).

Targeting of chromatin readers: a novel strategy used by the Shigella flexneri virulence effector OspF to reprogram transcription

December 28, 2014

In this microreview, the authors discuss the article "Shigella flexneri targets the HP1γ subcode through the phosphothreoninelyase OspF" by Harouz et al. (2014), EMBO J, 22 : 2606-2622.