Publications by authors named "Cristina de Castro"

Understanding the molecular mechanisms which drive and modulate host-pathogen interactions are essential when designing effective therapeutic and diagnostic approaches aimed at controlling infectious diseases. Certain large and giant viruses have recently been discovered as components of the human virome, yet little is known about their interactions with the host immune system. We have dissected the role of viral N-linked glycans during the interaction between the glycoproteins from six chloroviruses (belonging to three chlorovirus classes: NC64A, SAG, and Osy viruses) and the representative carbohydrate-binding receptors of the innate immune system.

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Article Synopsis
  • Capsular polysaccharide (CPS) from the bacterial pathogen Acinetobacter baumannii is a key factor in its virulence, specifically the KL58 variant produced by the strain MRSN 31468.
  • The CPS structure is characterized as a branched tetrasaccharide containing various sugar units, including glucose, galactose, N-acetyl-galactosamine, and a unique acid, indicating complex biosynthesis processes.
  • The study identified specific genes responsible for synthesizing components of CPS, noting that an acetyltransferase linked to a prophage may influence its structural modifications, while a related CPS variant contains a different epimer not present in MRSN 31468.
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Protein A075L is a β-xylosyltransferase that participates in producing the core of the N-glycans found in VP54, the major viral capsid protein of Paramecium bursaria chlorella virus-1 (PBCV-1). In this study, we present an X-ray crystallographic analysis of the apo form of A075L, along with its complexes with the sugar donor and with a trisaccharide acceptor. The protein structure shows a typical GT-B folding, with two Rossmann-like fold domains, in which the acceptor substrate binds to the N-terminal region, and the nucleotide-sugar donor binds to the C-terminal region.

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is one of the bacterial agents responsible for bovine respiratory disease (BRD). The capability of to form a biofilm may contribute to the development of chronic BRD infection by making the bacteria more resistant to host innate immunity and antibiotics. To improve therapy and prevent BRD, a greater understanding of the association between surface components and biofilm formation is needed.

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Ruminococcus gnavus is a prevalent member of the human gut microbiota and over-represented in inflammatory bowel diseases. R. gnavus ATCC 29149 was previously shown to produce a pro-inflammatory exopolysaccharide (EPS) referred to here as glucorhamnan-I or EPS.

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Article Synopsis
  • The cell-envelope of Gram-negative bacteria contains lipopolysaccharides (LPS) that activate the innate immune system via Toll-Like Receptors (TLRs), particularly TLR4 and TLR2.
  • Akkermansia muciniphila, a beneficial intestinal bacterium, has a unique form of LPS called lipooligosaccharide (LOS) that lacks an O-polysaccharide repeating unit and presents unusual structural features.
  • The study shows that A. muciniphila LOS elicits a stronger anti-inflammatory response by activating TLR2 over TLR4, potentially explaining its positive effects on the host's health.
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Glycosylation is the most prominent modification important for vaccines and its specific pattern depends on several factors that need to be considered when developing a new biopharmaceutical. Tailor-made glycosylation can be exploited to develop more effective and safer vaccines; for this reason, a deep understanding of both glycoengineering strategies and glycans structures and functions is required. In this review we discuss the recent advances concerning glycoprotein expression systems and the explanation of glycans immunomodulation mechanisms.

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Article Synopsis
  • - Innate immune cells play a crucial role in fighting tumors, and their function can be influenced by beneficial bacteria found in food.
  • - The specific bacterial strain Lactiplantibacillus plantarum IMB19 enhances antitumor immunity in mouse models, primarily through its capsular heteropolysaccharide, which activates immune pathways.
  • - This strain reprograms tumor-related macrophages to promote robust T cell responses while also capturing iron in the tumor environment, potentially leading to cancer cell death and improved treatment strategies using "oncobiotics."
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The mimivirus 1.2 Mb genome was shown to be organized into a nucleocapsid-like genomic fiber encased in the nucleoid compartment inside the icosahedral capsid. The genomic fiber protein shell is composed of a mixture of two GMC-oxidoreductase paralogs, one of them being the main component of the glycosylated layer of fibrils at the surface of the virion.

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Moraxella nonliquefaciens is a commensal of the human upper respiratory tract (URT) but on rare occasions is recovered in cases of ocular, septic and pulmonary infections. Hence there is interest in the pathogenic determinants of M. nonliquefaciens, of which outer membrane (OM) structures such as fimbriae and two capsular polysaccharide (CPS) structures, →3)-β-D-GalpNAc-(1→5)-β-Kdop-(2→ and →8)-α-NeuAc-(2→, have been reported in the literature.

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The species- and clone-specific susceptibility of cells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycosylation-dependent phage-WTA interactions in the opportunistic pathogen and in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a new WTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses.

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Enterococcus faecium, a gram-positive opportunistic pathogen, has become a major concern for nosocomial infections due to its resistance to several antibiotics, including vancomycin. Finding novel alternatives for treatment prevention, such as vaccines, is therefore crucial. In this study, we used various techniques to discover a novel capsular polysaccharide.

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Moraxella ovis is a Gram-negative bacterium isolated from sheep conjunctivitis cases and is a rare isolate of infectious bovine keratoconjunctivitis (IBK). This species is closely related to M. bovoculi, another species which can also be isolated from IBK, or cattle upper respiratory tract (URT).

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Archaea are microorganisms that comprise a distinct branch of the universal tree of life and which are best known as extremophiles, residing in a variety of environments characterized by harsh physical conditions. One seemingly universal trait of Archaea is the ability to perform N-glycosylation. At the same time, archaeal N-linked glycans present variety in terms of both composition and architecture not seen in the parallel eukaryal or bacterial processes.

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The need to protect human and environmental health and avoid the widespread use of substances obtained from nonrenewable sources is steering research toward the discovery and development of new molecules characterized by high biocompatibility and biodegradability. Due to their very widespread use, a class of substances for which this need is particularly urgent is that of surfactants. In this respect, an attractive and promising alternative to commonly used synthetic surfactants is represented by so-called biosurfactants, amphiphiles naturally derived from microorganisms.

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Asparagine-linked protein glycosylations (N-glycosylations) are one of the most abundant post-translational modifications and are essential for various biological phenomena. Herein, we describe the isolation, structural determination, and chemical synthesis of the N-glycan from the hyperthermophilic archaeon Thermococcus kodakarensis. The N-glycan from the organism possesses a unique structure including myo-inositol, which has not been found in previously characterized N-glycans.

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Methicillin-resistant (MRSA), a major human pathogen, uses the prophage-encoded gene as an important immune evasion factor. TarP glycosylates wall teichoic acid (WTA) polymers, major surface antigens, to impair WTA immunogenicity and impede host defence. However, phages appear to be restricted to only a few MRSA clonal lineages, including clonal complexes (CC) 5 and 398, for unknown reasons.

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Lipopolysaccharides (LPSs) are the main components of the external leaflet of the outer membrane of Gram-negative bacteria. They exert multiple functions, starting from conferring stability to the bacterial membrane to mediating the interaction of the microbe with the external environment. The composition and the structure of LPSs present tremendous diversity even within bacteria of the same species, and for this reason, the determination of the structure of these molecules is crucial because it can provide information on the motifs key for the virulence of a pathogen or that are associated to a bacterium of the commensal or beneficial microbiota.

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Halobacterium salinarum, a halophilic archaeon that grows at near-saturating salt concentrations, provided the first example of N-glycosylation outside Eukarya. Yet, almost 50 years later, numerous aspects of such post-translational protein processing in this microorganism remain to be determined, including the architecture of glycoprotein-bound glycans. In the present report, nuclear magnetic resonance spectroscopy was used to define a tetrasaccharide N-linked to both archaellins, building blocks of the archaeal swimming device (the archaellum), and the S-layer glycoprotein that comprises the protein shell surrounding the Hbt.

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Viruses are a heterogeneous ensemble of entities, all sharing the need for a suitable host to replicate. They are extremely diverse, varying in morphology, size, nature, and complexity of their genomic content. Typically, viruses use host-encoded glycosyltransferases and glycosidases to add and remove sugar residues from their glycoproteins.

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Akkermansia muciniphila is an intestinal symbiont known to improve the gut barrier function in mice and humans. Various cell envelope components have been identified to play a critical role in the immune signaling of A. muciniphila, but the chemical composition and role of peptidoglycan (PG) remained elusive.

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Article Synopsis
  • Scientists found that giant viruses have special proteins that help them make and process sugars.
  • They studied how these viruses create a sugary layer around themselves, discovering that they have many more genes for this than other viruses.
  • This research helps us understand how these giant viruses survive better in places where they compete with other germs for the same living space.
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Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. MA-1D has a 339-kb genome encoding ca. 366 proteins and 11 tRNAs.

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Structural determination of carbohydrates is mostly performed by liquid-state NMR, and it is a demanding task because the NMR signals of these biomolecules explore a rather narrow range of chemical shifts, with the result that the resonances of each monosaccharide unit heavily overlap with those of others, thus muddling their punctual identification. However, the full attribution of the NMR chemical shifts brings great advantages: it discloses the nature of the constituents, the way they are interconnected, in some cases their absolute configuration, and it paves the way to other and more sophisticated analyses. The purpose of this review is to provide a practical guide into this challenging subject.

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