Review, Reviews

Integrins in disguise – mechanosensors in Saccharomyces cerevisiae as functional integrin analogues

Tarek Elhasi1 and Anders Blomberg1

This article shows that although yeast lack integrin-like proteins, they possess WSC- and MID-type mechanosensors that functionally resemble integrins in animal cells, playing a role in sensing external mechanical stimuli and activating the conserved PKC1-SLT1 cell wall integrity pathway, with potential implications for understanding mechanosensing in yeast biology.

Bacterial maze runners reveal hidden diversity in chemotactic performance

M. Mehdi Salek1,#, Francesco Carrara1,#, Vicente Fernandez1 and Roman Stocker1

This article comments on work published by Salek et al. (Nat Commun, 2019), which combined microfluidic experiments with mathematical modeling to demonstrate that even in clonal populations, bacteria are individuals with different abilities to climb chemical gradients.

Beyond cells – The virome in the human holobiont

Rodrigo García-López1,2,3, Vicente Pérez-Brocal1,2,3 and Andrés Moya1,2,3

This article provides an overview of viromics—viral metagenomics—and its evolution, highlighting the complexity and dynamic nature of viruses beyond their traditional view as pathogens. It acknowledges the technological advancements in molecular biology and sequencing that have allowed the field to grow, while also noting that viromic research still faces significant challenges and is not as developed as bacterial metagenomics. The review underscores the importance of viruses in various ecosystems, their role in shaping the genetic landscape, and their potential impact, and looks forward to future directions in viromic research.

Laundry and textile hygiene in healthcare and beyond

Dirk P. Bockmühl1, Jan Schages1 and Laura Rehberg1

This article shows that while institutional laundering is regulated to ensure hygiene, the trend towards energy-efficient washing at lower temperatures raises concerns about the antimicrobial efficacy of domestic laundering, with a focus on addressing microbial contamination in both clinical and home settings.

Bacterial pathogens under high-tension: Staphylococcus aureus adhesion to von Willebrand factor is activated by force

Felipe Viela1, Pietro Speziale2,3, Giampiero Pietrocola2 and Yves F. Dufrêne1,4

This article comments on work published by Viela et al (mBio, 2019), which shows that the bacterial cell surface protein A to the large plasma glycoprotein von Willebrand factor interaction is tightly regulated by mechanical force.

Yeast AP-1 like transcription factors (Yap) and stress response: a current overview

Claudina Rodrigues-Pousada1, Frédéric Devaux2, Soraia M. Caetano1, Catarina Pimentel1, Sofia da Silva1, Ana Carolina Cordeiro1 and Catarina Amaral1

This review summarizes current understanding of the eight Yap transcription factors in Saccharomyces cerevisiae, detailing their activation by specific stress conditions and discussing their function and evolution across various fungal species.

Septin clearance from the division site triggers cytokinesis in budding yeast

Davide Tamborrini1 and Simonetta Piatti1

This article comments on work published by Tamborrini et al (Nat Commun., 2019), which shows that septin displacement during splitting is an essential prerequisite for contractile actomyosin ring constriction during mitosis.

The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging

Taylor N. Tibbs1,#, Lacey R. Lopez1,#, and Janelle C. Arthur1,2,3

This article shows that the microbiota is crucial for immune system development and that its relationship with the immune system during aging and the pathogenesis of age-related diseases, including cancer, needs further research to inform disease treatment and prevention.

Ser/Thr protein phosphatases in fungi: structure, regulation and function

Joaquín Ariño1, Diego Velázquez1 and Antonio Casamayor1

In this work we present the members of this family in S. cerevisiae and other fungal species, and review the most recent findings concerning their regulation and the roles they play in the most diverse aspects of cell biology.

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The metabolites of lactic acid bacteria: classification, biosynthesis and modulation of gut microbiota

February 8, 2023

Lactic acid bacteria (LAB) are ubiquitous microorganisms that can colonize the intestine and participate in the physiological metabolism of the host. In this review, we summarize the metabolites of LAB and their influence on the intestine as well as the underlying regulatory mechanisms and their impact on human health.

Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy

November 15, 2022

Prostate cancer (PC) can be kept in check by androgen deprivation therapy (ADT, usually with the androgen synthesis inhibitor abiraterone acetate or the androgen receptor antagonist such as enzalutamide) until the tumor evolves to castration-resistant prostate cancer (CRPC). The transition of hormone-sensitive PC (HSPC) to CPRC has been explained by cancer cell-intrinsic resistance mechanisms. Recent data indicate that this transition is also marked by cancer cell-extrinsic mechanisms such as the failure of ADT-induced PC immunosurveillance, which depends on the presence of immunostimulatory bacteria in the gut. Moreover, intestinal bacteria that degrade drugs used for ADT, as well as bacteria that produce androgens, can interfere with the efficacy of ADT. Thus, specific bacteria in the gut serve as a source of testosterone, which accelerates prostate cancer progression, and men with CRPC exhibit an increased abundance of such bacteria with androgenic functions. In conclusion, the response of PC to ADT is profoundly influenced by the composition of the microbiota with its immunostimulatory, immunosuppressive and directly ADT-subversive elements.

Occurrence and potential mechanism of holin-mediated non-lytic protein translocation in bacteria

September 23, 2022

Holins are generally believed to generate large membrane lesions that permit the passage of endolysins across the cytoplasmic membrane of prokaryotes, ultimately resulting in cell wall degradation and cell lysis. However, there are more and more examples known for non-lytic holin-dependent secretion of proteins by bacteria, indicating that holins somehow can transport proteins without causing large membrane lesions. Phage-derived holins can be used for a non-lytic endolysin translocation to permeabilize the cell wall for the passage of secreted proteins. In addition, clostridia, which do not possess the Tat pathway for transport of folded proteins, most likely employ non-lytic holin-mediated transport also for secretion of toxins and bacteriocins that are incompatible with the general Sec pathway. The mechanism for non-lytic holin-mediated transport is (...)

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. (...)

Pirates of the haemoglobin

February 18, 2022

Not all treasure is silver and gold; for pathogenic bacteria, iron is the most precious and the most pillaged of metallic elements. Iron is essential for the survival and growth of all life; however free iron is scarce for bacteria inside human hosts. As a mechanism of defence, humans have evolved ways to store iron so as to render it inaccessible for invading pathogens, such as keeping the metal bound to iron-carrying proteins. For bacteria to survive within humans, they must therefore evolve counters to this defence to compete with these proteins for iron binding, or directly steal iron from them. (...)

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, (...)

Endomembrane remodeling and dynamics in Salmonella infection

December 27, 2021

Salmonellae are bacteria that cause moderate to severe infections in humans, depending on the strain and the immune status of the infected host. These pathogens have the particularity of residing in the cells of the infected host. They are usually found in a vacuolar compartment that the bacteria shape with the help of effector proteins. Following invasion of a eukaryotic cell, the bacterial vacuole undergoes maturation characterized by changes in localization, composition and morphology. In particular, membrane tubules stretching over the microtubule cytoskeleton are formed from the bacterial vacuole. Although these tubules do not occur in all infected cells, they are functionally important and promote intracellular replication. This review focuses on the role and significance of membrane compartment remodeling observed in infected cells and the bacterial and host cell pathways involved.

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