Publications by authors named "Fernando Navarro-Garcia"

Enteropathogenic (EPEC) strains are subdivided into typical (tEPEC) and atypical (aEPEC) according to the presence or absence of a virulence-associated plasmid called pEAF. Our research group has previously demonstrated that two aEPEC strains, 0421-1 and 3991-1, induce an increase in mucus production in a rabbit ileal loop model . This phenomenon was not observed with a tEPEC prototype strain.

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Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown.

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Plasmid-encoded toxin (Pet) is an autotransporter protein of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, important in the pathogenicity of . The gene was initially found in the enteroaggregative (EAEC) virulence plasmid, pAA2. Although this virulence factor was initially described in EAEC, an intestinal pathotype, may also be present in other pathotypes, including extraintestinal pathogenic strains (ExPEC).

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Serine protease autotransporters of Enterobacteriaceae (SPATE) constitute a superfamily of virulence factors, resembling the trypsin-like superfamily of serine proteases. SPATEs accomplish multiple functions associated to disease development of their hosts, which could be the consequence of SPATE cleavage of host cell components. SPATEs have been divided into class-1 and class-2 based on structural differences and biological effects, including similar substrate specificity, cytotoxic effects on cultured cells, and enterotoxin activity on intestinal tissues for class-1 SPATEs, whereas most class-2 SPATEs exhibit a lectin-like activity with a predilection to degrade a variety of mucins, including leukocyte surface O-glycoproteins and soluble host proteins, resulting in mucosal colonization and immune modulation.

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Article Synopsis
  • Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by a mutant form of Lamin A called progerin, leading to premature aging.
  • Recent studies show that HGPS cells have issues with protein export due to the CRM1 pathway, and inhibiting this pathway with a drug called LMB can improve cell health by reducing senescence.
  • In this study, LMB not only enhances mitochondrial function in HGPS cells but also promotes mitochondrial biogenesis and mitophagy, making it a potential treatment strategy for HGPS and related diseases involving mitochondrial dysfunction.
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Background: Genetic/genomic testing (GGT) are useful tools for improving health and preventing diseases. Still, since GGT deals with sensitive personal information that could significantly impact a patient's life or that of their family, it becomes imperative to consider Ethical, Legal and Social Implications (ELSI). Thus, ELSI studies aim to identify and address concerns raised by genomic research that could affect individuals, their family, and society.

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The interaction of enteroaggregative Escherichia coli (EAEC) strains with the colonic gut mucosa is characterized by the ability of the bacteria to form robust biofilms, to bind mucin, and induce a local inflammatory response. These events are mediated by a repertoire of five different aggregative adherence fimbriae variants (AAF/I-V) typically encoded on virulence plasmids. In this study, we report the production in EAEC strains of a new YehD fimbriae (YDF), which is encoded by the chromosomal gene cluster yehABCD, also present in most E.

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A hallmark of enteroaggregative (EAEC) infection is the formation of an intestinal biofilm, which comprises a mucus layer with immersed bacteria. Pic is an autotransporter secreted by EAEC, and other pathotypes, and has been involved in two apparently contradictory phenotypes, as a mucus secretagogue and as a mucinase. Here, we investigated this Pic dual activity, mucus secretagogue capability and mucinolytic activity, in human goblet cells that secrete MUC2 and MUC5AC.

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β-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery-Dreifuss muscular dystrophy (EDMD).

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Shiga-toxin-producing (STEC) has become an important pathogen that can cause diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS) in humans. Recent reports show that the type VI secretion system (T6SS) from EHEC is required to produce infection in a murine model and its expression has been related to a higher prevalence of HUS. In this work, we use bioinformatics analyses to identify the core genes of the T6SS and compared the differences between these components among the two published genomes for EHEC O157:H7 strain EDL933.

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Pet and EspC are toxins secreted by enteroaggregative (EAEC) and enteropathogenic (EPEC) diarrheagenic pathotypes, respectively. Both toxins are members of the Serine Protease Autotransporters of (SPATEs) family. Pet and EspC are important virulence factors that produce cytotoxic and enterotoxic effects on enterocytes.

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Enteropathogenic Escherichia coli (EPEC) infection causes a histopathological lesion including recruitment of F-actin beneath the attached bacteria and formation of actin-rich pedestal-like structures. Another important target of EPEC is the tight junction (TJ), and EspF induces displacement of TJ proteins and increased intestinal permeability. Previously, we determined that an EPEC strain lacking EspF did not cause TJ disruption; meanwhile, pedestals were located on the TJ and smaller than those induced by the wild-type strain.

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Bacterial pathogens utilize a myriad of mechanisms to invade mammalian hosts, damage tissue sites, and evade the immune system. One essential strategy of Gram-negative bacteria is the secretion of virulence factors through both inner and outer membranes to reach a potential target. Most secretion systems are harbored in mobile elements including transposons, plasmids, pathogenicity islands, and phages, and is one of the more versatile bacteria adopting this genetic information by horizontal gene transfer.

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Aim: The aim of this work was to identify, characterize and evaluate the pathogenic role of mucinolytic activity released by Naegleria fowleri.

Materials & Methods: Zymograms, protease inhibitors, anion exchange chromatography, MALDI-TOF-MS, enzymatic assays, Western blot, and confocal microscopy were used to identify and characterize a secreted mucinase; inhibition assays using antibodies, dot-blots and mouse survival tests were used to evaluate the mucinase as a virulence factor.

Results: A 94-kDa protein with mucinolytic activity was inducible and abolished by p-hydroxymercuribenzoate.

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The type 3 secretion system (T3SS) is essential for bacterial virulence through delivering effector proteins directly into the host cytosol. Here, we identified an alternative delivery mechanism of virulence factors mediated by the T3SS, which consists of the association of extracellularly secreted proteins from bacteria with the T3SS to gain access to the host cytosol. Both EspC, a protein secreted as an enteropathogenic (EPEC) autotransporter, and YopH, a protein detected on the surface of , require a functional T3SS for host cell internalization; here we provide biophysical and molecular evidence to support the concept of the EspC translocation mechanism, which requires (i) an interaction between EspA and an EspC middle segment, (ii) an EspC translocation motif (21 residues that are shared with the YopH translocation motif), (iii) increases in the association and dissociation rates of EspC mediated by EspA interacting with EspD, and (iv) an interaction of EspC with the EspD/EspB translocon pore.

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Cytolethal distending toxins (CDTs), encoded by genes, have DNase activity leading to cellular and nuclear distension, resulting in irreversible cell cycle arrest and apoptosis of target cells. -positive strains have been isolated from children with diarrhoea. There is, however, scant information on the prevalence and clinical presentation of diarrhoeal disease caused by these strains.

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Inflammatory response is key for the host defense against diarrheagenic and contributes to the pathogenesis of the disease but there is not a comparative study among different diarrheagenic pathotypes. We analyzed the inflammatory response induced by five diarrheagenic pathotypes in a HT-29 cell infection model. The model was unified to reproduce the pathogenesis of each pathotype.

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The intestinal epithelium consists of a single cell layer, which is a critical selectively permeable barrier to both absorb nutrients and avoid the entry of potentially harmful entities, including microorganisms. Epithelial cells are held together by the apical junctional complexes, consisting of adherens junctions, and tight junctions (TJs), and by underlying desmosomes. TJs lay in the apical domain of epithelial cells and are mainly composed by transmembrane proteins such as occludin, claudins, JAMs, and tricellulin, that are associated with the cytoplasmic plaque formed by proteins from the MAGUK family, such as ZO-1/2/3, connecting TJ to the actin cytoskeleton, and cingulin and paracingulin connecting TJ to the microtubule network.

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Unlabelled: Enteropathogenic Escherichia coli (EPEC) has the ability to antagonize host apoptosis during infection through promotion and inhibition of effectors injected by the type III secretion system (T3SS), but the total number of these effectors and the overall functional relationships between these effectors during infection are poorly understood. EspC produced by EPEC cleaves fodrin, paxillin, and focal adhesion kinase (FAK), which are also cleaved by caspases and calpains during apoptosis. Here we show the role of EspC in cell death induced by EPEC.

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Most autotransporter passenger domains, regardless of their diversity in function, fold or are predicted to fold as right-handed β-helices carrying various loops that are presumed to confer functionality. Our goal here was to identify the subdomain (loop) or amino acid sequence of the Pet passenger domain involved in the receptor binding site on the host cell for Pet endocytosis. Here, we show that d1 and d2 subdomains, as well as the amino acid sequence linking the subdomain d2 and the adjacent β-helix (PDWET), are not required for Pet secretion through the autotransporter system and that none of our deletion mutants altered the predicted long right-handed β-helical structure.

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Autotransporter proteins (AT) are associated with bacterial virulence attributes. Originally identified in enteroaggregative Escherichia coli (EAEC), Shigella flexneri 2a and uropathogenic E. coli, the serine protease Pic is one of these AT.

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A major outbreak caused by Escherichia coli of serotype O104:H4 spread throughout Europe in 2011. This large outbreak was caused by an unusual strain that is most similar to enteroaggregative E. coli (EAEC) of serotype O104:H4.

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Pathogens are able to breach the intestinal barrier, and different bacterial species can display different abilities to colonize hosts and induce inflammation. Inflammatory response studies induced by enteropathogens as Escherichia coli are interesting since it has acquired diverse genetic mobile elements, leading to different E. coli pathotypes.

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Enteroaggregative and uropathogenic Escherichia coli, Shigella flexneri 2a, and the hybrid enteroaggregative/Shiga toxin-producing E. coli strain (O104:H4) are important pathogens responsible for intestinal and urinary tract infections, as well as sepsis and hemolytic uremic syndrome. They have in common the production of a serine protease called Pic.

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Enteropathogenic Escherichia coli (EPEC) is classified as typical (tEPEC) or atypical (aEPEC) based on the presence or absence of the E. coli adherence factor plasmid (pEAF), respectively. The hallmark of EPEC infection is the formation of the attaching and effacing (A/E) lesions on the gut mucosa.

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