Raquel

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    [Triunfo de la Iglesia ] [Material gráfico] / Iosephus Vergara Inv. et delin. ; Joach. Giner sc. Val. año 1752
    ([Valentiae : apud viduam Hieronymi Conejos : vendense ... en casa de Salvador Fauli ... ; y en Madrid : en casa de D. Francisco Assensio ..., 2012-11-30) Vergara, José; Raquel; Giner Grau, Joaquín
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    WadD, a New Brucella Lipopolysaccharide Core Glycosyltransferase Identified by Genomic Search and Phenotypic Characterization
    (NCBI, 2018) Cloeckaert, A. (Axel); Miguel, M.J. (María Jesús) de; Salvador-Bescós, M. (Miriam); Moriyon, I. (Ignacio); Zygmunt, M. (Michel); Gil-Ramirez, Y. (Yolanda); Zuñiga-Ripa, A. (Amaia); Muñoz, P. (Pilar); Iriarte-Cilveti, M. (Maite); Martinez-Gomez, E. (Estrella); Raquel
    Brucellosis, an infectious disease caused by Brucella, is one of the most extended bacterial zoonosis in the world and an important cause of economic losses and human suffering. The lipopolysaccharide (LPS) of Brucella plays a major role in virulence as it impairs normal recognition by the innate immune system and delays the immune response. The LPS core is a branched structure involved in resistance to complement and polycationic peptides, and mutants in glycosyltransferases required for the synthesis of the lateral branch not linked to the O-polysaccharide (O-PS) are attenuated and have been proposed as vaccine candidates. For this reason, the complete understanding of the genes involved in the synthesis of this LPS section is of particular interest. The chemical structure of the Brucella LPS core suggests that, in addition to the already identified WadB and WadC glycosyltransferases, others could be implicated in the synthesis of this lateral branch. To clarify this point, we identified and constructed mutants in 11 ORFs encoding putative glycosyltransferases in B. abortus. Four of these ORFs, regulated by the virulence regulator MucR (involved in LPS synthesis) or the BvrR/BvrS system (implicated in the synthesis of surface components), were not required for the synthesis of a complete LPS neither for virulence or interaction with polycationic peptides and/or complement. Among the other seven ORFs, six seemed not to be required for the synthesis of the core LPS since the corresponding mutants kept the O-PS and reacted as the wild type with polyclonal sera. Interestingly, mutant in ORF BAB1_0953 (renamed wadD) lost reactivity against antibodies that recognize the core section while kept the O-PS. This suggests that WadD is a new glycosyltransferase adding one or more sugars to the core lateral branch. WadD mutants were more sensitive than the parental strain to components of the innate immune system and played a role in chronic stages of infection. These results corroborate and extend previous work indicating that the Brucella LPS core is a branched structure that constitutes a steric impairment preventing the elements of the innate immune system to fight against Brucella
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    The identification of wadB, a new glycosyltransferase gene, confirms the branched structure and the role in virulence of the lipopolysaccharide core of Brucella abortus
    (2014) Moriyon, I. (Ignacio); Palacios-Chaves, L. (Leyre); Gil-Ramirez, Y. (Yolanda); Arce-Gorvel, V. (Vilma); Zuñiga-Ripa, A. (Amaia); Hanniffy, S. (Sean); Iriarte-Cilveti, M. (Maite); Raquel; Grillo, M.J. (María Jesús)
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    Rev1 wbdR tagged vaccines against Brucella ovis
    (Springer Science and Business Media LLC, 2019) Miguel, M.J. (María Jesús) de; Salvador-Bescós, M. (Miriam); Moriyon, I. (Ignacio); Zuñiga-Ripa, A. (Amaia); Aragón-Aranda, B. (Beatriz); Muñoz, P. (Pilar); Martinez-Gomez, E. (Estrella); Raquel
    Sheep brucellosis is a worldwide extended disease caused by B. melitensis and B. ovis, two species respectively carrying smooth or rough lipopolysaccharide. Vaccine B. melitensis Rev1 is used against B. melitensis and B. ovis but induces an anti-smooth-lipopolysaccharide response interfering with B. melitensis serodiagnosis, which precludes its use against B. ovis where B. melitensis is absent. In mice, Rev1 deleted in wbkC (Brucella lipopolysaccharide formyltransferase) and carrying wbdR (E. coli acetyl-transferase) triggered antibodies that could be diferentiated from those evoked by wild-type strains, was comparatively attenuated and protected against B. ovis, suggesting its potential as a B. ovis vaccine.
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    Prevalence and risk factors of brucellosis among febrile patients attending a community hospital in south western Uganda
    (NCBI, 2018) Bagenda, F. (Fred); Bonnet, M. (Maryline); Zuñiga-Ripa, A. (Amaia); Boum, Y. (Yap); Migisha, R. (Richard); Raquel; Nyehangane, D. (Dan); Page, A.L. (Anne Laure)
    Human brucellosis, a chronic disease contracted through contact with animals and consuption of unpasteurized dairy products is underreported in limited-resource countries. This cross-sectional study aimed to determine the prevalence and risk factors of brucellosis among febrile patients attending a community hospital in South western Uganda. A questionnaire that captured socio-demographic, occupational and clinical data was administered. Blood samples were tested for Brucella antibodies using Rose Bengal Plate Test (RBPT) and blood culture with standard aerobic BACTEC bottle was done. Of 235 patients enrolled, prevalence of brucellosis (RBPT or culture confirmed) was 14.9% (95%CI 10.6-20.1) with a culture confrmation in 4.3% of the participants. The factors independently associated with brucellosis were consumption of raw milk (aOR 406.15, 95% CI 47.67-3461.69); history of brucellosis in the family (aOR 9.19, 95% CI 1.98-42.54); and selling hides and skins (aOR 162.56, 95% CI 2.86-9256.31). Hepatomegaly (p < 0.001), splenomegaly (p = 0.018) and low body mass index (p = 0.032) were more common in patients with brucellosis compared to others. Our findings reveal a high prevalence of brucellosis among febrile patients and highlight a need for implementing appropiate tests, public awareness activities and vaccination of animals to control and eliminate the disease.
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    The prevalence of brucellosis and bovine tuberculosis in ruminants in Sidi Kacem Province, Morocco
    (NCBI, 2018) Hattendorf, J. (Jan); Moriyon, I. (Ignacio); Azami, H.Y. (Hind Yahyaoui); Zinsstag, J. (Jakob); Ducrotoy, M.J. (Marie J.); Welburn, S.C. (Susan C.); Zuñiga-Ripa, A. (Amaia); Muñoz, P. (Pilar); Thrusfield, M. (Mike); Bryssinckx, W. (Ward); Bouslikhane, M. (Mohammed); Mick, V. (Virginie); Raquel
    Bovine tuberculosis (BTB) and brucellosis are major endemic zoonoses in ruminants in Morocco that impact on both animal and human health. This study presents an assessment of the epidemiological and socioeconomic burden of bacterial zoonoses in Sidi Kacem Province in Northern Morocco from a cross-sectional survey of 125 cattle and/or small ruminantowning households. In total, 1082 sheep and goats were examined from 81 households. The single intradermal comparative cervical test to screen for bovine tuberculosis was undertaken on 1194 cattle from 123 households and all cattle were blood sampled. Cattle and small ruminant sera were tested for brucellosis using the standard Rose Bengal Test (sRBT) and the modified Rose Bengal Test (mRBT). Bacteriology was performed on 21 milk samples obtained from cattle that were seropositive for brucellosis for isolation and phenotyping of circulating Brucella strains. Individual and herd prevalence for BTB in cattle of 20.4% (95% CI 18%-23%) and 57.7% (95% CI 48%-66%), respectively, were observed in this study. The prevalence of brucellosis in cattle at individual and herd level was 1.9% (95% CI 1.2%-2.8%) and 9% (95% CI 4.5%-1.5%), respectively. Brucella pathogens were isolated from three cattle milk samples and were identified as B. abortus using Bruceladder (R) multiplex PCR and B. abortus biovar 1 by classical phenotyping. All small ruminants were seronegative to sRBT, two were positive to mRBT. A higher risk of BTB and brucellosis was observed in cattle in intensive livestock systems, in imported and crossed breeds and in animals from larger herds (>15). The three risk factors were usually present in the same herds, leading to higher transmission risk and persistence of both zoonoses. These results highlight the importance of implementing control strategies for both BTB and brucellosis to reduce productivity losses and the risk of transmission to humans. Prioritising control for BTB and brucellosis in intensive livestock production systems is essential for human and animal health.
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    Specific inhibition of diverse pathogens in human cells by synthetic microRNA-like oligonucleotides inferred from RNAi screens
    (National Academy of Sciences, 2014) Rämö, P. (Pauli); Dehio, C. (Christoph); Helenius, A. (Ari); Casanova, A. (Alain); Andritschke, D. (Daniel); Daga, N. (Neha); Dilling, S. (Sabrina); Franceschini, A. (Andrea); Emmenlauer, M. (Mario); Low, S.H. (Shyan Huey); Pelkmans, L. (Lucas); Kaufmann, A. (Andreas); Raquel; Meier, R. (Roger); Mering, C. (Christian) von; Kreibich, S. (Saskia); Hardt, W.D. (Wolf Dietrich)
    Systematic genetic perturbation screening in human cells remains technically challenging. Typically, large libraries of chemically synthesized siRNA oligonucleotides are used, each designed to degrade a specific cellular mRNA via the RNA interference (RNAi) mechanism. Here, we report on data from three genome-wide siRNA screens, conducted to uncover host factors required for infection of human cells by two bacterial and one viral pathogen. We find that the majority of phenotypic effects of siRNAs are unrelated to the intended “on-target” mechanism, defined by full complementarity of the 21-nt siRNA sequence to a target mRNA. Instead, phenotypes are largely dictated by “off-target” effects resulting from partial complementarity of siRNAs to multiple mRNAs via the “seed” region (i.e., nucleotides 2–8), reminiscent of the way specificity is determined for endogenous microRNAs. Quantitative analysis enabled the prediction of seeds that strongly and specifically block infection, independent of the intended on-target effect. This prediction was confirmed experimentally by designing oligos that do not have any on-target sequence match at all, yet can strongly reproduce the predicted phenotypes. Our results suggest that published RNAi screens have primarily, and unintentionally, screened the sequence space of microRNA seeds instead of the intended on-target space of protein-coding genes. This helps to explain why previously published RNAi screens have exhibited relatively little overlap. Our analysis suggests a possible way of identifying “seed reagents” for controlling phenotypes of interest and establishes a general strategy for extracting valuable untapped information from past and future RNAi screens.
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    The fast-growing Brucella suis Biovar 5 depends on phosphoenolpyruvatecCarboxykinase and pyruvate phosphate dikinase but not on Fbp and GlpX fructose-1,6-bisphosphatases or isocitrate lyase for full virulence in laboratory models
    (NCBI, 2018) Miguel, M.J. (María Jesús) de; Moriyon, I. (Ignacio); Zuñiga-Ripa, A. (Amaia); Muñoz, P. (Pilar); Lázaro-Antón, L. (Leticia); Iriarte-Cilveti, M. (Maite); Letesson, J.J. (Jean Jacques); Raquel; Barbier, T. (Thibault)
    Bacteria of the genus Brucella infect a range of vertebrates causing a worldwide extended zoonosis. The best-characterized brucellae infect domestic livestock, behaving as stealthy facultative intracellular parasites. This stealthiness depends on envelope molecules with reduced pathogen-associated molecular patterns, as revealed by the low lethality and ability to persist in mice of these bacteria. Infected cells are often engorged with brucellae without signs of distress, suggesting that stealthiness could also reflect an adaptation of the parasite metabolism to use local nutrients without harming the cell. To investigate this, we compared key metabolic abilities of Brucella abortus 2308 Wisconsin (2308W), a cattle biovar 1 virulent strain, and B. suis 513, the reference strain of the ancestral biovar 5 found in wild rodents. B. suis 513 used a larger number of C substrates and showed faster growth rates in vitro, two features similar to those of B. microti, a species phylogenomically close to B. suis biovar 5 that infects voles. However, whereas B. microti shows enhanced lethality and reduced persistence in mice, B. suis 513 was similar to B. abortus 2308W in this regard. Mutant analyses showed that B. suis 513 and B. abortus 2308W were similar in that both depend on phosphoenolpyruvate synthesis for virulence but not on the classical gluconeogenic fructose-1,6-bisphosphatases Fbp-GlpX or on isocitrate lyase (AceA). However, B. suis 513 used pyruvate phosphate dikinase (PpdK) and phosphoenolpyruvate carboxykinase (PckA) for phosphoenolpyruvate synthesis in vitro while B. abortus 2308W used only PpdK. Moreover, whereas PpdK dysfunction causes attenuation of B. abortus 2308W in mice, in B. suis, 513 attenuation occurred only in the double PckA-PpdK mutant. Also contrary to what occurs in B. abortus 2308, a B. suis 513 malic enzyme (Mae) mutant was not attenuated, and this independence of Mae and the role of PpdK was confirmed by the lack of attenuation of a double Mae-PckA mutant. Altogether, these results decouple fast growth rates from enhanced mouse lethality in the brucellae and suggest that an Fbp-GlpX-independent gluconeogenic mechanism is ancestral in this group and show differences in central C metabolic steps that may reflect a progressive adaptation to intracellular growth.
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    The identification of wadB, a new glycosyltransferase gene, confirms the branched structure and the role in virulence of the lipopolysaccharide core of Brucella abortus
    (2014) Moriyon, I. (Ignacio); Palacios-Chaves, L. (Leyre); Gil-Ramirez, Y. (Yolanda); Arce-Gorvel, V. (Vilma); Zuñiga-Ripa, A. (Amaia); Hanniffy, S. (Sean); Iriarte-Cilveti, M. (Maite); Raquel; Grillo, M.J. (María Jesús)
    Brucellosis is a worldwide extended zoonosis caused by Brucella spp. These gram-negative bacteria are not readily detected by innate immunity, a virulence-related property largely linked to their surface lipopolysaccharide (LPS). The role of the LPS lipid A and O-polysaccharide in virulence is well known. Moreover, mutation of the glycosyltransferase gene wadC of Brucella abortus, although not affecting O-polysaccharide assembly onto the lipid-A core section causes a core oligosaccharide defect that increases recognition by innate immunity. Here, we report on a second gene (wadB) encoding a LPS core glycosyltransferase not involved in the assembly of the O-polysaccharide-linked core section. As compared to wild-type B. abortus, a wadB mutant was sensitive to bactericidal peptides and non-immune serum, and was attenuated in mice and dendritic cells. These observations show that as WadC, WadB is also involved in the assembly of a branch of Brucella LPS core and support the concept that this LPS section is a virulence-related structure.
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    Corrigendum: genetic and phenotypic characterization of the etiological agent of canine orchiepididymitis smooth brucella sp. BCCN84.3
    (Frontiers Media SA, 2019) Suárez-Esquivel, M. (Marcela); Cloeckaert, A. (Axel); Chacon-Diaz, C. (Carlos); Moriyon, I. (Ignacio); Gonnet, M. (Mathieu); Víquez-Ruiz, E. (Eunice); Campos, E. (Elena); Zygmunt, M. (Michel); Thomson, N.R. (Nicholas R.); Aragón-Aranda, B. (Beatriz); Muñoz, P. (Pilar); Blasco, J.M. (J. M.); Baker, K.S. (Kate S.); Moreno, E. (Edgardo); Ruíz-Villalobos, N. (Nazareth); Guzman-Verri, C. (Caterina); Raquel
    In the original article, there was an error. In the Funding statement is written that MZ was granted with a fellowship from SEP, Universidad de Costa Rica. The correct Initials are MS-E.