Review, Reviews

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

Tiziana Cervelli1, Samuele Lodovichi1, Francesca Bellè1 and Alvaro Galli1

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

Gukui Chen1 and Haihua Liang1

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

Muna A. Khan1 and Boris Görke1

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

Christophe Viret1, Aurore Rozières1, Rémi Duclaux-Loras1, Gilles Boschetti1, Stéphane Nancey1 and
Mathias Faure1,2

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

Chengjun Cao1 and Chaoyang Xue1,2

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

Arijit Bhattacharya1, Sophia Bigot2, Prasad Kottayil Padmanabhan2, Angana Mukherjee2, Adriano Coelho3, Philippe Leprohon2, Barbara Papadopoulou2 and Marc Ouellette2

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

Jyoti P. Gurung1, Murat Gel2,3 and Matthew A. B. Baker1,3

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

Maria Joao Azevedo1,2,3,4, Maria de Lurdes Pereira1,5, Ricardo Araujo2,3,6, Carla Ramalho3,7,8, Egija Zaura4 and Benedita Sampaio-Maia1,2,3

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

Giulia Pontarollo1, Klytaimnistra Kiouptsi1 and Christoph Reinhardt1,2

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.

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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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