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(...)
The effect of multiple sclerosis therapy on gut microbiota dysbiosis: a longitudinal prospective study
April 6, 2024
The gut microbiota, a complex ecosystem with various immune functions, plays a significant role in MS, and its response to different treatments is highlighted in this study. In clinical practice, maintaining a healthy microbiota is crucial for individuals with MS.
Comparison of microbial communities and the profile of sulfate-reducing bacteria in patients with ulcerative colitis and their association with bowel diseases: a pilot study
March 14, 2024
Considerable evidence has accumulated regarding the molecular relationship between gut microbiota (GM) composition and the onset (clinical presentation and prognosis) of ulcerative colitis UC. Our findings highlight, among other observations, significant variations in the gut microbial composition among patients with varying disease severity and activity.
Replicative aging in yeast involves dynamic intron retention patterns associated with mRNA processing/export and protein ubiquitination
February 27, 2024
Saccharomyces cerevisiae has yielded relevant insights into some of the basic mechanisms of organismal aging. Among these are genomic instability, oxidative stress, caloric restriction and mitochondrial dysfunction. Our work uncovers a previously unexplored layer of the transcriptional program of yeast aging and, more generally, expands the knowledge on the occurrence of alternative splicing in baker´s yeast.
Predictable regulation of survival by intratumoral microbe-immune crosstalk in patients with lung adenocarcinoma
February 19, 2024
Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.
The last two transmembrane helices in the APC-type FurE transporter act as an intramolecular chaperone essential for concentrative ER-exit
January 5, 2024
FurE is a H+ symporter specific for the cellular uptake of uric acid, allantoin, uracil, and toxic nucleobase analogues in the fungus Aspergillus nidulans. Being member of the NCS1 protein family, FurE is structurally related to the APC-superfamily of transporters.