Microreviews

Host-bacteria metabolic crosstalk drives S. aureus biofilm

Kira L. Tomlinson1 and Sebastián A. Riquelme1

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.

When the pandemic opts for the lockdown: Secretion system evolution in the cholera bacterium

Francis J. Santoriello1,2 and Stefan Pukatzki1,2

This article comments on work published by Santoriello et al. (Nat Comm, 2020), which demonstrates that the T6SS island Auxiliary Cluster 3 (Aux3) is unique to pandemic strains of V. cholerae.

Maintaining phagosome integrity during fungal infection: do or die?

Mabel Yang1, Glenn F.W. Walpole1,2 and Johannes Westman1

This article refers to the paper "Lysosome Fusion Maintains Phagosome Integrity during Fungal Infection" by Westman et al. (Cell Host Microbe, 2020), which shows that macrophages respond to pathogen growth by expanding the phagosome membrane through a calcium-dependent mechanism involving lysosome insertion, maintaining membrane integrity and preventing rupture.

A novel antibacterial strategy: histone and antimicrobial peptide synergy

Leora Duong1, Steven P. Gross2,3 and Albert Siryaporn1,3

This article refers to the study "Mammalian histones facilitate antimicrobial synergy by disrupting the bacterial proton gradient and chromosome organization" by Doolin et al. (Nat Comm, 2020) that shows that histones enhance the antimicrobial activity of peptides, disrupt bacterial membranes, and inhibit transcription, offering new insights into natural antimicrobial mechanisms.

Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum

Jack D. Adderley1 and Christian Doerig1

This article refers to the study "Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention" by Adderley et al. (Nat Commun, 2020) that investigates how Plasmodium falciparum malaria parasites influence red blood cells. By tracking hanges in over 800 human proteins at different parasite stages they confirmed activation of the PAK-MEK pathway and discovered significant changes, particularly during the trophozoite stage. This suggests that kinases activated by the infection could be targeted for new antimalarial therapies.

A new role for proteins subunits of RNase P: stabilization of the telomerase holoenzyme

P. Daniela Garcia1 and Virginia A. Zakian2

This article refers to the study "Stability and Nuclear Localization of Yeast Telomerase Depend on Protein Components of RNase P/MRP", by Garcia et al. (Nat Commun, 2020), showing that 3 essential proteins in Saccharomyces cerevisiae are vital for telomerase assembly and nuclear localization. In their mutants, telomerase is less mature, and telomeres are shorter. TLC1 is properly folded but remains in the cytoplasm, rather than moving to the nucleus, where it maintains telomeres.

Lipid droplet biogenesis from specialized ER subdomains

Vineet Choudhary1 and Roger Schneiter2

This article refers to the paper "Seipin and Nem1 establish discrete ER subdomains to initiate yeast lipid droplet biogenesis" by Choudhary et al. (J Cell Biol, 2020), which deals with the formation of lipid droplets (LDs) at specific ER sites marked by the proteins Fld1 and Nem1. These proteins recruit enzymes such as Lro1 and Dga1 to initiate fat storage. Together, Fld1 and Nem1 define where LDs form by organising key proteins and lipids needed for their biogenesis.

A broad-spectrum antibiotic adjuvant SLAP-S25: one stone many birds

Meirong Song1 and Kui Zhu1

This article refers to the study "A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens" by Song et al. (Nat Microbiol, 2020), which deals with the growing threat of antibiotic resistance, with few new drugs being developed for decades. The study found that the peptide SLAP-S25 enhances the efficacy of several antibiotics against resistant Gram-negative bacteria by disrupting their membranes, thereby increasing drug uptake. This suggests that bacterial membranes are promising targets for new antibiotic adjuvants.

Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins

Mehdi Kabani1

This article relates to the study "Glucose availability dictates the export of the soluble and prion forms of Sup35p via periplasmic or extracellular vesicles" by Kabani et al. (Mol Microbiol, 2020) that provides compelling evidence that yeast prions, such as Sup35p in its infectious [PSI⁺] state, can be exported via both extracellular vesicles (EVs) and periplasmic vesicles (PVs), with this export being modulated by environmental glucose levels. The discovery that prion particles are released in high amounts through PVs during glucose starvation adds a new dimension to our understanding of prion transmission and opens up fascinating possibilities for exploring vesicle-mediated spread of protein aggregates in neurodegenerative diseases using yeast as a model system.

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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, (...)

Lipid and fatty acid metabolism in trypanosomatids

October 6, 2021

This work reviews specific aspects of lipid and fatty acid metabolism in the protozoan parasites T. brucei, T. cruzi, and Leishmania spp., as well as the pathways that have been explored for the development of new chemotherapies.

Using microbial metalo-aminopeptidases as targets in human infectious diseases

August 9, 2021

This Review highlights the relevant roles of microbial metalo-aminopeptidases in bacteria and protozoa that could be targeted for therapeutic purposes.

Understanding the pathogenesis of infectious diseases by single-cell RNA sequencing

August 4, 2021

This work highlights recent remarkable advances in single-cell RNA sequencing technologies and their applications in the investigation of host-pathogen interactions. Current challenges and potential prospects for disease treatment are discussed as well.

Exploring absent protein function in yeast: assaying post translational modification and human genetic variation

July 2, 2021

This review discusses the applicability of yeast systems to investigate absent human protein function with a specific focus on the impact of protein variation on protein-protein interaction modulation.

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.

Mechanisms underlying lactic acid tolerance and its influence on lactic acid production in Saccharomyces cerevisiae

April 14, 2021

This article reviews the manner in which Saccharomyces cerevisiae deals with the accumulation of lactic acid as a singular stress factor as well as in combination with other stresses. In addition, different methods to improve lactic acid tolerance in S. cerevisiae using targeted and non-targeted engineering methods are discussed.

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