Microreviews

Mnemons: encoding memory by protein super-assembly

Fabrice Caudron and Yves Barral

This article comments on work published by Caudron and Barral (Cell, 2013), which proposes that polyQ- and polyN-based elements, termed mnemons, act as cellular memory devices to encode previous environmental conditions.

Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose

Johan H. van Heerden1,3,4, Meike T. Wortel1,3,4, Frank J. Bruggeman1,4, Joseph J. Heijnen2,3, Yves J.M. Bollen4,5, Robert Planqué6, Josephus Hulshof6, Tom G. O’Toole7, S. Aljoscha Wahl2,3 and Bas Teusink1,3,4

This article comments on work published by van Heerden et al. (Science, 2014), which demonstrates that the startup of glycolysis exhibits two dynamic fates: a proper, functional, steady state or the imbalanced state described above. Both states are stable, attracting states, and the probability distribution of initial states determines the fate of a yeast cell exposed to glucose.

Intersubunit communications within KaiC hexamers contribute the robust rhythmicity of the cyanobacterial circadian clock

Yohko Kitayama1, Taeko Nishiwaki-Ohkawa1,2 and Takao Kondo1

This article comments on work published by Kitayama et al. (Nat Comm, 2013), which suggests that intersubunit communication precisely synchronizes KaiC subunits to avoid dephasing, and contributes to the robustness of circadian rhythms in cyanobacteria.

Building a flagellum in biological outer space

Lewis D. B. Evans, Colin Hughes and Gillian M. Fraser

This article comments on work published by Evans et al. (Nature, 2013), which presents a simple and elegant transit mechanism in which growth is powered by the subunits themselves as they link head-to-tail in a chain that is pulled through the length of the growing structure to the tip. This new mechanism answers an old question and may have resonance in other assembly processes.

A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation

Jelena Ostojić1, Jean-Paul di Rago2,3, Geneviève Dujardin1,*

This article comments on a study by Ostojić et al. (Cell Metabolism, 2013), which has uncovered a regulatory loop by which the biogenesis of a major enzyme of the OXPHOS pathway, the respiratory complex III, is coupled to the energy producing activity of the mitochondria.

Stalling autophagy: a new function for Listeria phospholipases

Ivan Tattoli1,2, Matthew T. Sorbara2, Dana J. Philpott2 and Stephen E. Girardin1,*

This article comments on a study biy Tattoli et al. (EMBO J, 2013), which demonstrated that Listeria PI-PLC and PC-PLC contribute to the bacterial escape from autophagy through a mechanism that involves direct inhibition of the autophagic flux in the infected cells

Identifying the assembly pathway of cyanophage inside the marine bacterium using electron cryo-tomography

Wei Dai1, Michael F. Schmid1, Jonathan A. King2, Wah Chiu1,*

Thiswork comments on a study by Dai et al. (Nature 2013) that illustrates that electron cryo-tomography is an approach whereby one can capture directly structural snapshots of transient phage assembly intermediates during maturation process. Such analysis can be generalizable not only to human viruses in human cells but also various molecular machines undergoing biological processes.

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Swimming faster despite obstacles: a universal mechanism behind bacterial speed enhancement in complex fluids

June 27, 2022

Bacteria constitute about 15% of global biomass and their natural environments often contain polymers and colloids, which show complex flow properties. It is crucial to study their motion in such environments to understand their growth and spreading as well as to design synthetic microswimmers for biomedical applications. Bacterial motion in complex viscous environments, although extensively studied over the past six decades, still remains poorly understood. In our recent study combining experimental data and theoretical analysis, we found a surprising similarity between bacterial motion in dilute colloidal suspensions and polymer solutions, which challenged the established view on the role of polymer dynamics on bacterial speed enhancement. We subsequently developed a physical model that provides a universal mechanism explaining bacterial speed enhancement (...)

A roadmap for designing narrow-spectrum antibiotics targeting bacterial pathogens

June 22, 2022

This comment discusses the article "Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile" by Cao et al. (2022, Nature).

Breaking the clip for cargo unloading from motor proteins: mechanism and significance

May 19, 2022

The mitochondrion is an essential organelle involved in ATP generation, lipid metabolism, regulation of calcium ions, etc. Therefore, it should be inherited properly by newly generated cells. In the budding yeast Saccharomyces cerevisiae, mitochondria are passed on to daughter cells by the motor protein, Myo2, on the actin cable. The mitochondria and Myo2 are connected via the adaptor protein Mmr1. After reaching daughter cells, mitochondria are released from the actin-myosin machinery and move dynamically. In our recent paper (Obara K et al. (2022), Nat Commun, doi:10.1038/s41467-022-29704-8), we demonstrated that the regulated proteolysis of Mmr1 is required for the unloading of mitochondria from Myo2 in daughter cells. Sequential post-translational modifications of Mmr1, i.e., phosphorylation followed by ubiquitination, are essential for Mmr1 degradation and mitochondrial release from Myo2. Defects in Mmr1 degradation cause stacking and deformation of mitochondria at the bud-tip and bud-neck, where Myo2 accumulates. Compared to wild-type cells, mutant cells with defects in Mmr1 degradation possess an elevated mitochondrial membrane potential and produce higher levels of reactive oxygen species (ROS), along with hypersensitivity to oxidative stress.

Fatty acid metabolism of Mycobacterium tuberculosis: A double-edged sword

February 28, 2022

Unlike other heterotrophic bacteria, Mycobacterium tuberculosis (Mtb) can co-catabolize a range of carbon sources simultaneously. Evolution of Mtb within host nutrient environment allows Mtb to consume the host’s fatty acids as a main carbon source during infection. The fatty acid-induced metabolic advantage greatly contributes to Mtb’s pathogenicity and virulence. Thus, the identification of key enzymes involved in Mtb’s fatty acid metabolism is urgently needed to aid new drug development. Two fatty acid metabolism enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and isocitrate lyase (ICL) have been intensively studied as promising drug targets, but recently, Quinonez et al. (mBio, doi: 10.1128/mbio.03559-21) highlighted a link between the fatty acid-induced dormancy-like state and drug tolerance. (...)

An ionophore breaks the multi-drug-resistance of Acinetobacter baumannii

February 15, 2022

Within intensive care units, multi-drug resistant Acinetobacter baumannii outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary A. baumannii pulmonary infection. In our recent paper (De Oliveira et al. (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant A. baumannii, (...)

The small bowel microbiome changes significantly with age and aspects of the ageing process

December 27, 2021

Gut microbiome changes have been associated with human ageing and implicated in age-related diseases including Alzheimer’s disease and Parkinson’s disease. However, studies to date have used stool samples, which do not represent the entire gut. Although more challenging to access, the small intestine plays critical roles in host metabolism and immune function. In this paper (Leite et al. (2021), Cell Reports, doi: 10.1016/j.celrep.2021.109765), we demonstrate significant differences in the small intestinal microbiome in older subjects, (...)

LasR-regulated proteases in acute vs. chronic lung infection: a double-edged sword

May 31, 2021

This article comments on work published by Hennemann et al. (PLoS Pathog, 2021), which observed that in Pseudomonas aeruginosa, functional loss of the quorum sensing transcriptional activator LasR in lasR variants results in impaired secreted protease production, leads to increased expression of the membrane-bound surface adhesion molecule mICAM-1 in the airway epithelium, and increases neutrophilic inflammation.

DNA polymerase III protein, HolC, helps resolve replication/transcription conflicts

May 6, 2021

This article comments on work published by Cooper et al. (mBio, 2021), which isolated and identified spontaneous suppressor mutants in a strain devoid of the holC gene, which encodes an accessory protein to the core clamp loader complex and is the only protein of the DNA polymerase III holoenzyme that binds to single-strand DNA binding protein.

Too much of a good thing: Overproduction of virulence factors impairs cryptococcal pathogenicity

April 20, 2021

This article comments on work published by Reuwsaat et al. (mBio, 2021), which identified the transcription factor Pdr802 as essential for Cryptococcus neoformans adaptation to and survival under host conditions both in vitro and in vivo.

Host-bacteria metabolic crosstalk drives S. aureus biofilm

April 19, 2021

This article comments on work published by Tomlinson et al. (Nat Comm, 2021), which demonstrates that Staphylococcus aureus induces the production of the immunoreglatory metabolite itaconate in airway immune cells by stimulating mitochondrial oxidant stress. Itaconate in turn inhibits S. aureus glycolysis and growth, and promoted carbon flux through bacterial metabolic pathways that support biofilm production.

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