Review, Reviews

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

Julia C. V. Reuwsaat1, Tamara L. Doering2, and Livia Kmetzsch1,3

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

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.

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

Arne Peetermans1,2, María R. Foulquié-Moreno1,2 and Johan M. Thevelein1,2,3

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.

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.

Biofilms by bacterial human pathogens: Clinical relevance – development, composition and regulation – therapeutical strategies

Adina Schulze1,#, Fabian Mitterer1,#, Joao P. Pombo1 and Stefan Schild1,2,3

This review focuses on bacterial biofilms formed by human pathogens, highlights their relevance for diverse diseases and discusses therapeutical intervention strategies targeting biofilms.

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.

Milestones in Bacillus subtilis sporulation research

Eammon P. Riley1, Corinna Schwarz2, Alan I. Derman2 and Javier Lopez-Garrido2

In this review, the foundational discoveries that shaped the sporulation field are discussed, from its origins to the present day, tracing a chronology that spans more than one hundred eighty years.

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.

Extracellular vesicles: An emerging platform in gram-positive bacteria

Swagata Bose1,#, Shifu Aggarwal1,#, Durg Vijai Singh1,2 and Narottam Acharya1

Extracellular vesicles (EVs) are secreted by both pathogenic and non-pathogenic bacteria to transfer biomolecules and facilitate intercellular communication. While EV secretion in gram-negative bacteria is well understood, less is known about gram-positive bacteria. This review explores the role of EVs involved in bacterial competition, survival, immune evasion, and infection of gram-positive bacteria and compares them to gram-negative counterparts.

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From the Uncharacterized Protein Family 0016 to the GDT1 family: Molecular insights into a newly-characterized family of cation secondary transporters

June 15, 2020

This review outlines how the formerly uncharacterized UPF0016 family, now known as the Gdt1 family, plays key roles in cation transport - especially Mn²⁺ - across species from bacteria to humans. These proteins are crucial for processes like glycosylation, photosynthesis, and calcium signaling, with functions linked to their localization in membranes such as the Golgi, chloroplast, and plasma membrane and by that highlighting their evolutionary conservation and physiological relevance, offering insights into their shared and distinct features across organisms.

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

June 15, 2020

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

June 2, 2020

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.

Regulation of Cdc42 for polarized growth in budding yeast

May 19, 2020

This review highlights how studies in budding yeast have revealed a biphasic mechanism of Cdc42 activation that governs cell polarity establishment, with implications for understanding similar processes in mammalian cells and the role of Cdc42 in aging.

Yeast-based assays for the functional characterization of cancer-associated variants of human DNA repair genes

May 18, 2020

This article highlights how the genetic tractability and conserved DNA repair pathways of yeast make it a powerful system for functionally characterizing human cancer-associated variants in DNA repair genes, aiding in risk assessment and therapeutic decision-making.

A novel c-di-GMP signal system regulates biofilm formation in Pseudomonas aeruginosa

April 23, 2020

This article relates to the study "The SiaA/B/C/D signaling network regulates biofilm formation in Pseudomonas aeruginosa" by Chen et al. (EMBO J, 2020) that reveals a novel signaling network encoded by the siaABCD operon in Pseudomonas aeruginosa that regulates biofilm and aggregate formation by controlling the diguanylate cyclase activity of SiaD through phosphorylation-dependent interactions with SiaC, highlighting a potential antimicrobial target.

A multifunctional small RNA binding protein for sensing and signaling cell envelope precursor availability in bacteria

April 15, 2020

This article relates to the study "Small RNA‐binding protein RapZ mediates cell envelope precursor sensing and signaling in Escherichia coli" by Khan et al. (EMBO J, 2020) that uncovers a complex regulatory network in E. coli where the RNA-binding protein RapZ functions as a sensor for GlcN6P, coordinating sRNA activity and a two-component system to maintain GlcN6P homeostasis and regulate cell envelope biosynthesis.

Regulation of anti-microbial autophagy by factors of the complement system

March 19, 2020

This review explores emerging evidence that components of the complement system, beyond their traditional immune roles, modulate autophagy - particularly xenophagy - thereby influencing cell-autonomous antimicrobial responses during host-pathogen interactions.

More than flipping the lid: Cdc50 contributes to echinocandin resistance by regulating calcium homeostasis in Cryptococcus neoformans

February 20, 2020

In this article, the authors comment on the study "A mechanosensitive channel governs lipid flippase-mediated echinocandin resistance in Cryptococcus neoformans" by Cao et al. (mBio, 2019), which uncovers a dual role for the lipid flippase subunit Cdc50 in Cryptococcus neoformans, linking lipid translocation and calcium signaling via its interaction with the mechanosensitive channel Crm1, thereby contributing to innate resistance against the antifungal drug caspofungin.

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.

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