Research, Research Articles
TL-532, a novel specific Toll-like receptor 3 agonist rationally designed for targeting cancers: discovery process and biological characterization
Sylvain Thierry1, Sarah Maadadi1, Aurore Berton1, Laura Dimier1, Clémence Perret1, Nelly Vey1, Saïd Ourfali2, Mathilde Saccas1, Solène Caron1, Mathilde Boucard-Jourdin1, Marc Colombel3, Bettina Werle1 and Marc Bonnin1
In the present study, we identified a new family of TLR3 agonists that activates myeloid cells, triggers the secretion of pro-inflammatory cytokines in both myeloid and cancer cells, and induces apoptosis specifically in cancer cells.
Acetate modulates the inhibitory effect of Lactobacillus gasseri against the pathogenic yeasts Candida albicans and Candida glabrata
Nuno A. Pedro1,2, Gabriela Fontebasso1,2, Sandra N. Pinto1,2, Marta Alves3 and Nuno P. Mira1,2
The results herein described advance the design of new anti-Candida therapies based on probiotics, in particular, those based on vaginal lactobacilli species, helping to reduce the significant burden that infections caused by Candida have today in human health.
D-Serine reduces the expression of the cytopathic genotoxin colibactin
Jennifer C. Hallam1,#, Sofia Sandalli1,#, Iris Floria1, Natasha C. A. Turner1, Min Tang-Fichaux2, Eric Oswald2,3, Nicky O’Boyle1,4 and Andrew J. Roe1
Sensing and responding to environmental cues and signalling molecules is crucial for bacterial survival. In this study we have identified a D-amino acid that has a strong regulatory effect on the pks genomic island which encodes for biosynthesis genes for the genotoxic compound colibactin.
A modular cloning (MoClo) toolkit for reliable intracellular protein targeting in the yeast Saccharomyces cerevisiae
Pavel Simakin1,#, Christian Koch1,# and Johannes M. Herrmann1
In this study, we describe an advanced Molecular cloning toolkit that is designed for the baker’s yeast Saccharomyces cerevisiae and optimized for the targeting of proteins of interest to specific cellular compartments.
The first taxonomic and functional characterization of human CAVD-associated microbiota
Lavinia Curini1,#, Brunilda Alushi2,#, Mary Roxana Christopher3, Simone Baldi1, Leandro Di Gloria4, Pierluigi Stefano5, Anna Laganà5, Luisa Iannone5, Herko Grubitzsch6, Ulf Landmesser7, Matteo Ramazzotti4, Elena Niccolai1,§, Alexander Lauten2,§ and Amedeo Amedei1,8,§
Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process. In this study, we aimed to investigate and characterize the presence of valvular microbiota and the associated immune response in human CAV samples originating from two European populations.
Cellular cholesterol licenses Legionella pneumophila intracellular replication in macrophages
Edna Ondari1,#, Ashley Wilkins1,#, Brian Latimer3, Ana-Maria Dragoi2,3 and Stanimir S. Ivanov1
Host membranes are inherently critical for niche homeostasis of vacuolar pathogens such as Legionella. One membrane component that is often subverted by vacuolar bacteria is cholesterol. We provide experimental evidence that cellular cholesterol promotes L. pneumophila replication within a membrane bound organelle in infected macrophages.
DadY (PA5303) is required for fitness of Pseudomonas aeruginosa when growth is dependent on alanine catabolism
Ronnie L. Fulton1 and Diana M. Downs1
Pseudomonas aeruginosa inhabits diverse environmental niches that can have varying nutrient composition. The ubiquity of this organism is facilitated by a metabolic strategy that preferentially utilizes low-energy, non-fermentable organic acids, such as amino acids, rather than the high-energy sugars preferred by many other microbes. The amino acid alanine is among the preferred substrates of P. aeruginosa. The dad locus encodes the constituents of the alanine catabolic pathway of P. aeruginosa. Physiological roles for DadR (AsnC-type transcriptional activator), DadX (alanine racemase), and DadA (D-amino acid dehydrogenase) have been defined in this pathway. An additional protein, PA5303, is encoded in the dad locus in P. aeruginosa. PA5303 is a member of the ubiquitous Rid protein superfamily and is designated DadY based on the data presented herein. (...)
Multiple genome analysis of Candida glabrata clinical isolates renders new insights into genetic diversity and drug resistance determinants
Pedro Pais1,2,3,#, Mónica Galocha1,2,3,#, Azusa Takahashi-Nakaguchi4, Hiroji Chibana4 and Miguel C. Teixeira1,2,3
The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as Candida species. Candida glabrata ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as PDR1 (azole resistance) or FKS1/2 (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of C. glabrata drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The(...)
Dry biocleaning of artwork: an innovative methodology for Cultural Heritage recovery?
April 15, 2021
This work proposes an innovative methodology based on applied biotechnology for the recovery of altered stonework: the "dry biocleaning", which envisages the use of dehydrated microbial cells without the use of free water or gel-based matrices.
Aeration mitigates endoplasmic reticulum stress in Saccharomyces cerevisiae even without mitochondrial respiration
March 31, 2021
This work demonstrates a scenario, in which aeration acts beneficially on Saccharmyces cerevisiae cells even under fermentative conditions.
Nutrient sensing and cAMP signaling in yeast: G-protein coupled receptor versus transceptor activation of PKA
October 12, 2020
The herein presented work supports a model, in which nutrient transceptors are evolutionary ancestors of GPCRs, employing a more primitive direct signaling mechanism compared to the indirect cAMP second-messenger signaling mechanism used by GPCRs for activation of PKA.
Novobiocin inhibits membrane synthesis and vacuole formation of Enterococcus faecalis protoplasts
August 10, 2020
In this study Tsuchikado et al. show that DNA replication is crucial for plasma membrane biosynthesis and vacuole formation in Enterococcus faecalis protoplasts. Novobiocin inhibits DNA replication, blocking cell enlargement and vacuole formation. Extended treatment prevents re-enlargement after removal.
Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast
July 20, 2020
RAD52 is a key protein in DNA repair and suppresses DNA damage in yeast; however, certain variants affecting BRCA2 mutations fail to correct HRR defects. This suggests that HsRAD52 aids multiple DNA repair mechanisms and could be targeted for use in treating BRCA2-deficient cancers.
Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage
April 24, 2020
This study reveals that conserved residues H3E73 and H4E53 in histones H3 and H4 play a crucial role in maintaining genome stability. Mutations at these sites increase recombinogenic DNA damage, likely due to replication-associated issues rather than transcriptional activity, highlighting their importance in DNA damage prevention and repair.
Broad-spectrum antifungal activities and mechanism of drimane sesquiterpenoids
March 12, 2020
This study identifies (-)-drimenol as a potent broad-spectrum antifungal agent effective against multiple pathogenic fungi, including drug-resistant strains, and reveals its mechanism of action involves disruption of fungal membranes and targeting Crk1-related pathways, with potential for structural optimization to enhance efficacy.
Stable and destabilized GFP reporters to monitor calcineurin activity in Saccharomyces cerevisiae
February 5, 2020
This study introduces GFP-based transcriptional reporters driven by a calcineurin-dependent response element, enabling real-time monitoring of calcineurin activity in live yeast cells for studying stress responses, aging, and antifungal drug screening.
The euchromatic histone mark H3K36me3 preserves heterochromatin through sequestration of an acetyltransferase complex in fission yeast
January 3, 2020
This study reveals that the loss of heterochromatin silencing in Set2-deficient cells is due to unrestrained Mst2C activity, highlighting the need for spatially restricted chromatin-modifying enzymes to maintain distinct chromatin states.