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5. Unprocessed snRNAs Are a Prognostic Biomarker and Correlate with a Poorer Prognosis in Colorectal Cancer.

Author

Escrich, Víctor, Romero-Aranda, Cristina, López, Rosario, de Toro, María, Metola, Ángela, Ezcurra, Begoña, Gómez-Orte, Eva, and Cabello, Juan

Subjects
PHYSICAL diagnosis, RESEARCH funding, T-test (Statistics), POLYMERASE chain reaction, COLORECTAL cancer, TUMOR markers, MAGNETIC resonance imaging, MANN Whitney U Test, DESCRIPTIVE statistics, MULTIVARIATE analysis, RNA, KAPLAN-Meier estimator, GENE expression profiling, QUALITY of life, STATISTICS, GENETIC mutation, SURVIVAL analysis (Biometry), DATA analysis software
Abstract

Simple Summary: Integrator-complex deregulation is involved in 8.3% of colorectal cancer cases. Lack of Integrator-complex function, measured by an increased level of unprocessed snRNA, is a prognostic biomarker and correlates with a poorer prognosis in colorectal cancer. Our results show that lack of Integrator-complex function (measured as level of snRNA processing) and not necessarily its expression level correlates with a poorer prognosis in colorectal-cancer patients. Population screening, combined with early typing of tumors, appears to be the most efficient way to increase patient survival. The human Integrator complex is a set of 15 subunits that mediates processing of small nuclear RNAs (snRNAs), and which later participates in splicing messenger RNAs (mRNAs). In addition, it controls the pause and release of RNA polymerase II (RNA pol II) at specific gene promoters in response to growth factors. Mutations in Integrator-complex subunit 6 (INTS6) are associated with different types of tumors. However, the INTS6 gene product does not have a significant prognostic value as a biomarker for tumor progression. Here we show that Integrator-complex deregulation is involved in 8.3% of the colorectal cancer cases diagnosed from the population screen carried out in La Rioja (Spain) from the years 2017 to 2019. Lack of Integrator-complex function, measured by an increased level of unprocessed snRNA, is a prognostic biomarker and correlates with a poorer prognosis in colorectal-cancer patients. The transcriptomic profile of all analyzed colorectal tumors shows a strong alteration of the metabolic state of tumor cells, which compromises standard energy production through mitochondrial respiration, known as the Warburg effect. Furthermore, there is a significant upregulation of genes involved in extracellular matrix organization and collagen rearrangement. This is consistent with tissue reorganization in a growing tumor forming a polyp. Crossing the molecular data generated in this study with the follow-up of patients from population screening indicates that population screening combined with early typing of tumors appears to be the most efficient way to increase patient survival. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Abstract P3-01-04: A real-world evidence study of everolimus plus endocrine therapy beyond CDK4/6 inhibitors for HR+/HER2- advanced breast cancer

Author

Sánchez-Bayona, Rodrigo, primary, Alva, Manuel, additional, López de sa, Alfonso, additional, Gilarranz, Yolanda Jerez, additional, Sánchez de torre, Ana, additional, Tolosa, Pablo, additional, de luna, Alicia, additional, López-Tarruella, Sara, additional, Lema, Laura, additional, Moreno, Fernando, additional, Echavarria, Isabel, additional, Madariaga, Ainhoa, additional, Benítez, Javier, additional, Herrero, Blanca, additional, Rey, Macarena, additional, Ortega, Justo, additional, Gámez, Salvador, additional, Modrego, Andrea, additional, Lozano, Rocío Martín, additional, Figuero-Pérez, Luis, additional, Jiménez, Roberto, additional, Sevilla, Marta González, additional, González, Irene, additional, Beranek, Marianela Bringas, additional, de toro, María, additional, Massarrah, Tatiana, additional, del Monte-Millán, María, additional, Pinardo, Marina, additional, Manso, Luis, additional, Bueno-Muiño, Coralia, additional, García-Sáenz, José Ángel, additional, Martín, Miguel, additional, and Ciruelos, Eva, additional

Published
2023
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17. Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral olfactory interactions

Author

Lachén-Montes, Mercedes, primary, Mendizuri, Naroa, additional, Ausín, Karina, additional, Echaide, Miriam, additional, Blanco, Ester, additional, Chocarro, Luisa, additional, de Toro, María, additional, Escors, David, additional, Fernández-Irigoyen, Joaquín, additional, Kochan, Grazyna, additional, and Santamaría, Enrique, additional

Published
2022
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18. Spread of bla CTX-M-9 and Other Clinically Relevant Resistance Genes, Such as mcr-9 and qnrA1 , Driven by IncHI2-ST1 Plasmids in Clinical Isolates of Monophasic Salmonella enterica Serovar Typhimurium ST34.

Author

Vázquez, Xenia, Fernández, Javier, Alkorta, Miriam, de Toro, María, Rodicio, M. Rosario, and Rodicio, Rosaura

Subjects
SALMONELLA enterica serovar typhimurium, SALMONELLA enterica serovar Typhi, PLASMIDS, WHOLE genome sequencing, BACTERIAL adaptation, GENES
Abstract

The monophasic 4,[5],12:i:-variant of Salmonella enterica serovar Typhimurium with sequence type ST34 has become one of the most prevalent non-typhoidal salmonellae worldwide. In the present study, we thoroughly characterized seven isolates of this variant detected in a Spanish hospital and selected based on cefotaxime resistance and cefoxitin susceptibility, mediated by blaCTX-M-9. For this, conventional microbiological techniques, together with whole genome sequencing performed with the Illumina platform, were applied. All selected isolates carried the resistance region RR or variants therein, and most also contained the SGI-4 genomic island. These chromosomal elements, typically associated with monophasic S. Typhimurium ST34, confer resistance to traditional antibiotics (ampicillin, streptomycin, sulfonamides, and tetracycline) and tolerance to heavy metals (mercury, silver, and copper). In addition, each isolate carried a large IncHI2-ST1 conjugative plasmid containing additional or redundant resistance genes. All harbored the blaCTX-M-9 gene responsible for cefotaxime resistance, whereas the qnrA1 gene mediating fluoroquinolone resistance was detected in two of the plasmids. These genes were embedded in ISCR1-bearing complex class 1 integrons, specifically In60-like and In36-like. The mcr-9 gene was present in all but one of the IncHI2-ST1 plasmids found in the analyzed isolates, which were nevertheless susceptible to colistin. Most of the resistance genes of plasmid origin clustered within a highly complex and variable region. The observed diversity results in a wide range of resistance phenotypes, enabling bacterial adaptation to selective pressure posed by the use of antimicrobials. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Genomic Analysis of Ciprofloxacin-Resistant Salmonella enterica Serovar Kentucky ST198 From Spanish Hospitals

Author

Vázquez, Xenia, primary, Fernández, Javier, additional, Bances, Margarita, additional, Lumbreras, Pilar, additional, Alkorta, Miriam, additional, Hernáez, Silvia, additional, Prieto, Elizabeth, additional, de la Iglesia, Pedro, additional, de Toro, María, additional, Rodicio, M. Rosario, additional, and Rodicio, Rosaura, additional

Published
2021
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22. The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

Author

López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodriguez, Paula, Bracho, Maria Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, de Marco, Griselda, García-González, Neris, Goig, Galo Adrian, Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martinez-Priego, Llúcia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, Jose Antonio, Bordoy, Antoni E., Canut-Blasco, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, Maria Luz, Costa-Alcalde, José J., de Toro, María, de Toro Peinado, Inmaculada, del Pozo, Jose Luis, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno Cardona, Concepción, González Galán, Verónica, Gonzalo Jiménez, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José Antonio, López-Causapé, Carla, López-Hontangas, José Luis, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, Maria Carmen, Pérez-Lago, Laura, Pérez-Ruiz, Mercedes, Piñeiro Vázquez, Luis, Rabella, Nuria, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Soriano, Alex, Tirado Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Pérez-Tur, Jordi, Catalán-Alonso, Pilar, Suárez González, Julia, Muñoz, Patricia, Ruiz-Rodríguez, Paula, Bracho, María Alma, Martínez Priego, Llúcia, Galán-Vendrell, Inmaculada, De Marco, Griselda, Ferrús-Abad, María Loreto, Carbó-Ramírez, Sandra, Nogueira, Jose Miguel, Camarena, Juan José, Martínez Expósito, Óscar, Antona Urieta, Nerea, Castelló-Abietar, Cristian, Rojo-Alba, Susana, Álvarez-Argüelles, Marta Elena, Melón, Santiago, Antuori, Adrián, Fernández-Navarro, Anabel, Lecaroz Agara, Maria Concepción, Gómez-González, Carmen, Aguirre-Quiñonero, Amaia, López-Mirones, José Israel, Fernández-Torres, Marina, Almela-Ferrer, Maria Rosario, Fregeneda-Grandes, Juan Miguel, Argüello, Héctor, Sorarrain, Ane, Trastoy, Rocío, Barbeito Castiñeiras, Gema, Coira, Amparo, Pérez del Molino, María Luisa, Aguilera, Antonio, Mediavilla Gradolph, Maria Concepción, Fernández-Alonso, Mirian, González-Recio, Oscar, Gutiérrez-Rivas, Mónica, Jiménez Clavero, Miguel Ángel, Ocete Mochón, María Dolores, Medina-Gonzalez, Rafael, Reina, Jordi, Gómez-Ruiz, Maria Dolores, Gonzalez-Barbera, Eva M., Molina, Antonio J., Fernandez-Villa, Tania, Martínez-Cameo, Nieves Felisa, Gracia-Grataloup, Yolanda, Tirado Balaguer, Maria Dolores, Gómez Alonso, Bárbara, Arjona Zaragozí, Francisco José, Chamizo López, Francisco Javier, Bordes-Benítez, Ana, Rabella, Núria, Navarro, Ferran, Miró, Elisenda, Simarro Córdoba, Encarnación, Lozano-Serra, Julia, Soriano, Álex, Roig Sena, Francisco Javier, Vanaclocha Luna, Hermelinda, Sanmartín, Isabel, García-Souto, Daniel, Pequeño-Valtierra, Ana, Tubio, Jose M. C., Temes, Javier, Rodríguez-Castro, Jorge, Santamarina García, Martín, Rodríguez-Iglesias, Manuel, Galán-Sanchez, Fátima, Rodríguez-Pallares, Salud, Azcona-Gutiérrez, José Manuel, Blasco-Alberdi, Miriam, Mayor, Alfredo, García-Basteiro, Alberto L., Moncunill, Gemma, Dobaño, Carlota, Cisteró, Pau, Mitjà, Oriol, González-Beiras, Camila, Vall-Mayans, Martí, Corbacho-Monné, Marc, Alemany, Andrea, Muñoz-Cuevas, Cristina, Rodríguez-Rodríguez, Guadalupe, Benito, Rafael, Algarate, Sonia, Bueno, Jessica, Vergara-Gómez, Andrea, Martínez, Miguel J., Vila, Jordi, Rubio, Elisa, Peiró-Mestres, Aida, Navero-Castillejos, Jessica, Posada, David, Valverde, Diana, Estévez, Nuria, Fernández-Silva, Iria, de Chiara, Loretta, Gallego-García, Pilar, Varela, Nair, Gómez-Pinedo, Ulises, Gozalo-Margüello, Mónica, Cano García, Maria Eliecer, Méndez-Legaza, José Manuel, Rodríguez-Lozano, Jesus, Siller, María, Pablo-Marcos, Daniel, Ruiz-García, Maria Montserrat, Galiana, Antonio, Sánchez-Almendro, Judith, Gascón Ros, Maria Isabel, Torregrosa-Hetland, Cristina Juana, Pastor Boix, Eva María, Cascales Ramos, Paloma, Garcinuño Enríquez, Pedro Luis, Raga Borja, Salvador, González Cantó, Julia, Martínez Macias, Olalla, de Salazar, Adolfo, Viñuela González, Laura, Chueca, Natalia, García, Federico, Gómez-Camarasa, Cristina, Farga Martí, Amparo, Falcón, Rocío, Domínguez-Márquez, Victoria, Planas, Anna M., Fernández-Cádenas, Israel, Marcos, Maria Ángeles, Ezpeleta, Carmen, Navascués, Ana, Miqueleiz Zapatero, Ana, Segovia, Manuel, Moreno-Docón, Antonio, Viedma, Esther, Recio Martínez, Raúl, Muñoz-Gallego, Irene, Gonzalez-Bodi, Sara, Folgueira, Maria Dolores, Mingorance, Jesús, Dahdouh, Elias, Lázaro-Perona, Fernando, Rodríguez-Tejedor, María, Romero-Gómez, María Pilar, García-Rodríguez, Julio, Galán, Juan Carlos, Rodríguez-Dominguez, Mario, Martínez-García, Laura, Abreu Di Berardino, Melanie, Ponce-Alonso, Manuel, González-Alba, Jose Maria, Sanz-Muñoz, Ivan, Pérez San José, Diana, Gil Fortuño, Maria, Bellido-Blasco, Juan B., Yagüe Muñoz, Alberto, Hernández Pérez, Noelia, Buj Jordá, Helena, Pérez Olaso, Óscar, González Praetorius, Alejandro, Martínez Ramírez, Nora Mariela, Ramírez Marinero, Aida, Padilla León, Eduardo, Vilas Basil, Alba, Canal Aranda, Mireia, Bernet Sánchez, Albert, Bellés Bellés, Alba, López González, Eric, Prats Sánchez, Iván, García-González, Mercè, Martínez-Lirola, Miguel José, Rodríguez Maresca, Manuel Ángel, Cabezas Fernández, Maria Teresa, Carrillo Gil, María Eugenia, Ventero Martín, Maria Paz, Molina Pardines, Carmen, Orta Mira, Nieves, Navarro Cots, María, Vidal Catalá, Inmaculada, García Nava, Isabel, Illescas Fernández-Bermejo, Soledad, Martínez-Alarcón, José, Torres-Narbona, Marta, Colmenarejo, Cristina, García-Agudo, Lidia, Pérez García, Jorge A., Yago López, Martín, Goberna Bravo, María Ángeles, Simón García, Victoria, Llop Furquet, Gonzalo, Iranzo Tatay, Agustín, Moreno-Marro, Sandra, Lozano Rodríguez, Noelia, Broseta Tamarit, Amparo, Badiola Díez, Juan José, Martínez-Ramírez, Amparo, Dopazo, Ana, Callejas, Sergio, Benguría, Alberto, Aguado, Begoña, Alcamí, Antonio, Bermejo Bermejo, Marta, Ramos-Ruíz, Ricardo, Fernández Soria, Víctor Manuel, Simón Soria, Fernando, Roig Cardells, Mercedes, Coscolla, Mireia, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, European Commission, Generalitat Valenciana, Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], D'Auria, Giuseppe [0000-0003-0672-2541], Gómez-Navarro, Inmaculada [0000-0002-5235-7365], Jiménez Serrano, Santiago [0000-0003-2917-6053], Aranzamendi Zaldumbide, Maitane [0000-0003-2432-7078], Boga, José Antonio [0000-0002-5500-9972], Bordoy, Antoni E. [0000-0002-1165-542X], Costa-Alcalde, José J. [0000-0002-1916-2216], Toro Peinado, Inmaculada de [0000-0002-8151-3275], López-Causapé, Carla [0000-0003-2228-2005], Martín, Vicente [0000-0003-0552-2804], Moreno-Muñoz, Rosario [0000-0002-0185-5612], Parra Grande, Mónica [0000-0002-8330-7467], Balaguer, María Dolores [0000-0003-3808-7300], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Ministerio de Ciencia (España), Generalitat Valenciana (España), Chiner-Oms, Álvaro, Ruiz-Rodríguez, Paula, D'Auria, Giuseppe, Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Aranzamendi Zaldumbide, Maitane, Boga, José Antonio, Bordoy, Antoni E., Costa-Alcalde, José J., Toro Peinado, Inmaculada de, López-Causapé, Carla, Martín, Vicente, Moreno-Muñoz, Rosario, Parra Grande, Mónica, Balaguer, María Dolores, Coscolla, Mireia, González-Candelas, Fernando, Comas, Iñaki, and Marimon, Jose Maria

Subjects
DYNAMICS, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Physical Distancing, Biology, Severity of Illness Index, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Pandemic, Quarantine, Genetics, Humans, Clade, Phylogeny, 030304 developmental biology, 0303 health sciences, Models, Statistical, SARS-CoV-2, Incidence (epidemiology), Incidence, Genetic variants, COVID-19, Genomics, New variant, Dynamics, Virus, 3. Good health, Spain, Communicable Disease Control, VIRUS, 030217 neurology & neurosurgery, Demography
Abstract

SeqCOVID-Spain consortium: Álvaro Chiner-Oms, Irving Cancino-Muñoz, Mariana G. López, Manuela Torres-Puente, Inmaculada Gómez-Navarro, Santiago Jiménez-Serrano, Jordi Pérez-Tur, Darío García de Viedma, Laura Pérez-Lago, Marta Herranz, Jon Sicilia, Pilar Catalán-Alonso, Julia Suárez González, Patricia Muñoz, Mireia Coscolla, Paula Ruiz-Rodríguez, Fernando González-Candelas, Iñaki Comas, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Llúcia Martínez Priego, Inmaculada Galán-Vendrell, Paula Ruiz-Hueso, Griselda De Marco, María Loreto Ferrús-Abad, Sandra Carbó-Ramírez, Giuseppe D’Auria, Galo Adrian Goig, Juan Alberola, Jose Miguel Nogueira, Juan José Camarena, David Navarro, Eliseo Albert, Ignacio Torres, Maitane Aranzamendi Zaldumbide, Óscar Martínez Expósito, Nerea Antona Urieta, María de Toro, María Pilar Bea-Escudero, Jose Antonio Boga, Cristian Castelló-Abietar, Susana Rojo-Alba, Marta Elena Álvarez-Argüelles, Santiago Melón, Elisa Martró, Antoni E. Bordoy, Anna Not, Adrián Antuori, Anabel Fernández-Navarro, Andrés Canut-Blasco, Silvia Hernáez Crespo, Maria Luz Cordón Rodríguez, Maria Concepción Lecaroz Agara, Carmen Gómez-González, Amaia Aguirre-Quiñonero, José Israel López-Mirones, Marina Fernández-Torres, Maria Rosario Almela-Ferrer, Ana Carvajal, Juan Miguel Fregeneda-Grandes, Héctor Argüello, Gustavo Cilla Eguiluz, Milagrosa Montes Ros, Luis Piñeiro Vázquez, Ane Sorarrain, José María Marimón, José J. Costa-Alcalde, Rocío Trastoy, Gema Barbeito Castiñeiras, Amparo Coira, María Luisa Pérez del Molino, Antonio Aguilera, Begoña Palop-Borrás, Inmaculada de Toro Peinado, Maria Concepción Mediavilla Gradolph, Mercedes Pérez-Ruiz, Mirian Fernández-Alonso, Jose Luis del Pozo, Oscar González-Recio, Mónica Gutiérrez-Rivas, Jovita Fernández-Pinero, Miguel Ángel Jiménez Clavero, Begoña Fuster Escrivá, Concepción Gimeno Cardona, María Dolores Ocete Mochón, Rafael Medina-Gonzalez, José Antonio Lepe, Verónica González Galán, Ángel Rodríguez-Villodres, Nieves Gonzalo Jiménez, Jordi Reina, Carla López-Causapé, Maria Dolores Gómez-Ruiz, Eva M. Gonzalez-Barbera, José Luis López-Hontangas, Vicente Martín, Antonio J. Molina, Tania Fernandez-Villa, Ana Milagro Beamonte, Nieves Felisa Martínez-Cameo, Yolanda Gracia-Grataloup, Rosario Moreno-Muñoz, Maria Dolores Tirado Balaguer, José María Navarro-Marí, Irene Pedrosa-Corral, Sara Sanbonmatsu-Gámez, Antonio Oliver, Mónica Parra Grande, Bárbara Gómez Alonso, Francisco José Arjona Zaragozí, Maria Carmen Pérez González, Francisco Javier Chamizo López, Ana Bordes-Benítez, Núria Rabella, Ferran Navarro, Elisenda Miró, Antonio Rezusta, Alexander Tristancho, Encarnación Simarro Córdoba, Julia Lozano-Serra, Lorena Robles Fonseca, Álex Soriano, Francisco Javier Roig Sena, Hermelinda Vanaclocha Luna, Isabel Sanmartín, Daniel García-Souto, Ana Pequeño-Valtierra, Jose M. C. Tubio, Javier Temes, Jorge Rodríguez-Castro, Martín Santamarina García, Manuel Rodríguez-Iglesias, Fátima Galán-Sanchez, Salud Rodríguez-Pallares, José Manuel Azcona-Gutiérrez, Miriam Blasco-Alberdi, Alfredo Mayor, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobaño, Pau Cisteró, Oriol Mitjà, Camila González-Beiras, Martí Vall-Mayans, Marc Corbacho-Monné, Andrea Alemany, Cristina Muñoz-Cuevas, Guadalupe Rodríguez-Rodríguez, Rafael Benito, Sonia Algarate, Jessica Bueno, Andrea Vergara-Gómez, Miguel J. Martínez, Jordi Vila, Elisa Rubio, Aida Peiró-Mestres, Jessica Navero-Castillejos, David Posada, Diana Valverde, Nuria Estévez, Iria Fernández-Silva, Loretta de Chiara, Pilar Gallego-García, Nair Varela, Ulises Gómez-Pinedo, Mónica Gozalo-Margüello, Maria Eliecer Cano García, José Manuel Méndez-Legaza, Jesus Rodríguez-Lozano, María Siller, Daniel Pablo-Marcos, Maria Montserrat Ruiz-García, Antonio Galiana, Judith Sánchez-Almendro, Maria Isabel Gascón Ros, Cristina Juana Torregrosa-Hetland, Eva María Pastor Boix, Paloma Cascales Ramos, Pedro Luis Garcinuño Enríquez, Salvador Raga Borja, Julia González Cantó, Olalla Martínez Macias, Adolfo de Salazar, Laura Viñuela González, Natalia Chueca, Federico García, Cristina Gómez-Camarasa, Amparo Farga Martí, Rocío Falcón, Victoria Domínguez-Márquez, Anna M. Planas, Israel Fernández-Cádenas, Maria Ángeles Marcos, Carmen Ezpeleta, Ana Navascués, Ana Miqueleiz Zapatero, Manuel Segovia, Antonio Moreno-Docón, Esther Viedma, Raúl Recio Martínez, Irene Muñoz-Gallego, Sara Gonzalez-Bodi, Maria Dolores Folgueira, Jesús Mingorance, Elias Dahdouh, Fernando Lázaro-Perona, María Rodríguez-Tejedor, María Pilar Romero-Gómez, Julio García-Rodríguez, Juan Carlos Galán, Mario Rodríguez-Dominguez, Laura Martínez-García, Melanie Abreu Di Berardino, Manuel Ponce-Alonso, Jose Maria González-Alba, Ivan Sanz-Muñoz, Diana Pérez San José, Maria Gil Fortuño, Juan B. Bellido-Blasco, Alberto Yagüe Muñoz, Noelia Hernández Pérez, Helena Buj Jordá, Óscar Pérez Olaso, Alejandro González Praetorius, Nora Mariela Martínez Ramírez, Aida Ramírez Marinero, Eduardo Padilla León, Alba Vilas Basil, Mireia Canal Aranda, Albert Bernet Sánchez, Alba Bellés Bellés, Eric López González, Iván Prats Sánchez, Mercè García-González, Miguel José Martínez-Lirola, Manuel Ángel Rodríguez Maresca, Maria Teresa Cabezas Fernández, María Eugenia Carrillo Gil, Maria Paz Ventero Martín, Carmen Molina Pardines, Nieves Orta Mira, María Navarro Cots, Inmaculada Vidal Catalá, Isabel García Nava, Soledad Illescas Fernández-Bermejo, José Martínez-Alarcón, Marta Torres-Narbona, Cristina Colmenarejo, Lidia García-Agudo, Jorge A. Pérez García, Martín Yago López, María Ángeles Goberna Bravo, Victoria Simón García, Gonzalo Llop Furquet, Agustín Iranzo Tatay, Sandra Moreno-Marro, Noelia Lozano Rodríguez, Amparo Broseta Tamarit, Juan José Badiola Díez, Amparo Martínez-Ramírez, Ana Dopazo, Sergio Callejas, Alberto Benguría, Begoña Aguado, Antonio Alcamí, Marta Bermejo Bermejo, Ricardo Ramos-Ruíz, Víctor Manuel Fernández Soria, Fernando Simón Soria & Mercedes Roig Cardells, The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re, This work was mainly funded by the Instituto de Salud Carlos III project COV20/00140, with additional funding by Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia project PID2019-104477RB-100, ERC StG 638553 and ERC CoG 101001038 to I.C., and BFU2017-89594R to F.G.C. M.C. is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and Generalitat Valenciana (Regional Government) project SEJI/2019/011. We gratefully acknowledge Hospital Universitari Vall d’Hebron, Instituto de Salud Carlos III, IrsiCaixa AIDS Research Lab and all the international researchers and institutions that submitted sequenced SARS-CoV-2 genomes to the GISAID’s EpiCov Database (Supplementary Table 1), as an important part of our analyses has been made possible by the sharing of their work. We also thank Unidad de Bioinformática y Estadística, Centro de Investigación Príncipe Felipe, for allowing us to use the Computer Cluster to perform some of the bioinformatic analysis.

Published
2021

24. Pathways for horizontal gene transfer in bacteria revealed by a global map of their plasmids

Author

Garcillán-Barcia, M. Pilar, Redondo-Salvo, Santiago, Fernández-López, Raúl, Ruiz, Raúl, Vielva, Luis, de Toro, María, Rocha, Eduardo, Garcillán-Barcia, M Pilar, de La Cruz, Fernando, Instituto de Biomedicina y Biotecnología de Cantabria [Santander, Espagne] (IBBTEC), Universidad de Cantabria [Santander], Centro de Investigación Biomédica de La Rioja (CIBIR), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was funded by grant BFU2017-86378-P from the Spanish MINECO, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Universidad de Cantabria, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Gene Transfer, Horizontal, Science, 030106 microbiology, General Physics and Astronomy, Virulence, Genomics, MESH: Algorithms, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Mobile elements, Bacterial genetics, 03 medical and health sciences, Plasmid, MESH: Plasmids, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Science, MESH: Phylogeny, Gene, Phylogeny, Genetics, Multidisciplinary, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], MESH: Genomics, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], General Chemistry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Gene Transfer, Horizontal, 030104 developmental biology, MESH: Gammaproteobacteria, Horizontal gene transfer, lcsh:Q, Plasmidome, Mobile genetic elements, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Algorithms, Gammaproteobacteria, Plasmids
Abstract

© The Author(s) 2020, Plasmids can mediate horizontal gene transfer of antibiotic resistance, virulence genes, and other adaptive factors across bacterial populations. Here, we analyze genomic composition and pairwise sequence identity for over 10,000 reference plasmids to obtain a global map of the prokaryotic plasmidome. Plasmids in this map organize into discrete clusters, which we call plasmid taxonomic units (PTUs), with high average nucleotide identity between its members. We identify 83 PTUs in the order Enterobacterales, 28 of them corresponding to previously described archetypes. Furthermore, we develop an automated algorithm for PTU identification, and validate its performance using stochastic blockmodeling. The algorithm reveals a total of 276 PTUs in the bacterial domain. Each PTU exhibits a characteristic host distribution, organized into a six-grade scale (I–VI), ranging from plasmids restricted to a single host species (grade I) to plasmids able to colonize species from different phyla (grade VI). More than 60% of the plasmids in the global map are in groups with host ranges beyond the species barrier., This work was funded by grant BFU2017-86378-P from the Spanish MINECO.

Published
2020
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28. Molecular Characteristics of Extraintestinal Pathogenic E. coli (ExPEC), Uropathogenic E. coli (UPEC), and Multidrug Resistant E. coli Isolated from Healthy Dogs in Spain. Whole Genome Sequencing of Canine ST372 Isolates and Comparison with Human Isolates Causing Extraintestinal Infections

Author

Flament-Simon, Saskia-Camille, primary, de Toro, María, additional, García, Vanesa, additional, Blanco, Jesús E., additional, Blanco, Miguel, additional, Alonso, María Pilar, additional, Goicoa, Ana, additional, Díaz-González, Juan, additional, Nicolas-Chanoine, Marie-Hélène, additional, and Blanco, Jorge, additional

Published
2020
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30. Holistic assessment of the microbiome dynamics in the substrates used for commercial champignon ( Agaricus bisporus ) cultivation

Author

Carrasco, Jaime, primary, García‐Delgado, Carlos, additional, Lavega, Rebeca, additional, Tello, María L., additional, De Toro, María, additional, Barba‐Vicente, Víctor, additional, Rodríguez‐Cruz, María S., additional, Sánchez‐Martín, María J., additional, Pérez, Margarita, additional, and Preston, Gail M., additional

Published
2020
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33. Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology

Author

Izco, María, primary, Blesa, Javier, additional, Schleef, Martin, additional, Schmeer, Marco, additional, Porcari, Riccardo, additional, Al-Shawi, Raya, additional, Ellmerich, Stephan, additional, de Toro, María, additional, Gardiner, Chris, additional, Seow, Yiqi, additional, Reinares-Sebastian, Alejandro, additional, Forcen, Raquel, additional, Simons, J. Paul, additional, Bellotti, Vittorio, additional, Cooper, J. Mark, additional, and Alvarez-Erviti, Lydia, additional

Published
2019
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34. Disruption of the Caenorhabditis elegans Integrator complex triggers a non-conventional transcriptional mechanism beyond snRNA genes

Author

Gómez-Orte, Eva, Sáenz-Narciso, Beatriz, Zheleva, Angelina, Ezcurra, Begoña, de Toro, María, López, Rosario, Gastaca, Irene, Nilsen, Hilde, Sacristán, María P., Schnabel, Ralf, Cabello, Juan, 0000-0001-6802-1746, 0000-0001-7211-2616, 0000-0003-3329-0203, 0000-0002-9069-395X, 0000-0003-2115-2663, 0000-0002-3835-0116, European Commission, Instituto de Estudios Riojanos, Fundación Rioja Salud, and South-Eastern Norway Regional Health Authority

Subjects
Cancer Research, Transcription, Genetic, Nematoda, Integrator complex, RNA polymerase II, Biochemistry, Animals, Genetically Modified, 0302 clinical medicine, RNA interference, RNA, Small Nuclear, Gene expression, Transcriptional regulation, RNA Processing, Post-Transcriptional, Genetics (clinical), Genes, Helminth, Regulation of gene expression, 0303 health sciences, biology, Small nuclear RNA, Transcriptional Control, Eukaryota, Animal Models, Cell biology, Up-Regulation, Nucleic acids, Genetic interference, Experimental Organism Systems, Gene Knockdown Techniques, Engineering and Technology, Epigenetics, RNA Polymerase II, Signal Transduction, Research Article, Integrators, lcsh:QH426-470, DNA transcription, Down-Regulation, Research and Analysis Methods, 03 medical and health sciences, Model Organisms, Genetics, Animals, Gene Regulation, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Non-coding RNA, Molecular Biology, Transcription factor, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Biology and life sciences, Organisms, Promoter, Invertebrates, lcsh:Genetics, Mutation, biology.protein, Animal Studies, Caenorhabditis, RNA, RNA, Helminth, Electronics, 030217 neurology & neurosurgery, Transcription Factors
Abstract

© 2019 Gómez-Orte et al., Gene expression is generally regulated by recruitment of transcription factors and RNA polymerase II (RNAP II) to specific sequences in the gene promoter region. The Integrator complex mediates processing of small nuclear RNAs (snRNAs) as well as the initiation and release of paused RNAP II at specific genes in response to growth factors. Here we show that in C. elegans, disruption of the Integrator complex leads to transcription of genes located downstream of the snRNA loci via a non-conventional transcription mechanism based on the lack of processing of the snRNAs. RNAP II read-through generates long chimeric RNAs containing snRNA, the intergenic region and the mature mRNA of the downstream gene located in sense. These chimeric sn-mRNAs remain as untranslated long non-coding RNAs, in the case of U1- and U2-derived sn-mRNAs, but can be translated to proteins in the case of SL-derived sn-mRNAs. The transcriptional effect caused by disruption of the Integrator complex is not restricted to genes located downstream of the snRNA loci but also affects key regulators of signal transduction such as kinases and phosphatases. Our findings highlight that these transcriptional alterations may be behind the correlation between mutations in the Integrator complex and tumor transformation., JC is funded by the European Refbio II program (EFA038_Momeneu) (refbio.eu/en/), Instituto de Estudios Riojanos (I.E.R.) and by the Rioja Salud Foundation (www.fundacionriojasalud.org). HN is funded by the South East Norway Regional Health Authority (grant No. 2015029).

Published
2019

39. Selection for antimicrobial resistance in foodborne pathogens through exposure to ultraviolet light and non-thermal atmospheric plasma decontamination techniques.

Author

Álvarez-Molina, Adrián, de Toro, María, Ruiz, Lorena, López, Mercedes, Prieto, Miguel, and Alvarez-Ordóñez, Avelino

Subjects
*DRUG resistance in microorganisms, *ULTRAVIOLET radiation, *NON-thermal plasmas, *FOOD pathogens, *COLISTIN, *TETRACYCLINES
Abstract

This study was aimed at assessing whether the repeated exposure of twelve strains of Salmonella spp., Escherichia coli and Listeria monocytogenes to the alternative non-thermal decontamination techniques ultraviolet light (UV-C) and non-thermal atmospheric plasma (NTAP) may cause the emergence of variants showing an increased resistance to clinically relevant antibiotics (ampicillin, cefotaxime, ciprofloxacin, gentamicin, streptomycin, tetracycline, erythromycin, vancomycin and colistin). UV-C and NTAP treatments were applied on the surface of inoculated BHI agar plates. Survivors were recovered and, after 24 hours growth in BHI broth, subjected again to the decontamination treatment and this was repeated for 10 consecutive cycles. A total of 174 strain/decontamination technique/antibiotic combinations were tested and 12 variant strains with an increased resistance to one of the antibiotics studied were identified, with increases in minimum inhibitory concentrations in MH broth ranging from 2 to 256 fold. The variant strains isolated for Salmonella spp. were further characterized through phenotypic screenings and whole genome sequencing (WGS) analyses. Most changes in susceptibility were observed for antibiotics that act at the level of protein synthesis (aminoglycosides, tetracyclines and glycylcyclines) or DNA replication (fluoroquinolones), as well as for polymyxins. No changes in resistance to ß-lactams were detected. WGS analyses showed the occurrence of sequence alterations in some antibiotic cellular targets (e.g. gyrA for ciprofloxacin-resistant variants; rpsL for a streptomycin-resistant variant), accompanied by variations in stress response regulators and membrane transporters likely involved in non-selective efflux of antibiotics, which altogether result in an increase of low/medium level in microbial resistance to several antibiotics. [ABSTRACT FROM AUTHOR]

Published
2020
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40. Effect of the diet type and temperature on theC. eleganstranscriptome

Author

Gómez-Orte, Eva, primary, Cornes, Eric, additional, Zheleva, Angelina, additional, Sáenz-Narciso, Beatriz, additional, de Toro, María, additional, Iñiguez, María, additional, López, Rosario, additional, San-Juan, Juan-Félix, additional, Ezcurra, Begoña, additional, Sacristán, Begoña, additional, Sánchez-Blanco, Adolfo, additional, Cerón, Julián, additional, and Cabello, Juan, additional

Published
2017
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44. Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages

Author

LS IRAS EEPI GRA (Gezh.risico-analyse), Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA-SIB, de Been, Mark, Lanza, Val F., de Toro, María, Scharringa, Jelle, Dohmen, Wietske, Du, Yu, Hu, Juan, Lei, Ying, Li, Ning, Tooming-Klunderud, Ave, Heederik, Dick J J, Fluit, Ad C., Bonten, Marc J M, Willems, Rob J L, de la Cruz, Fernando, van Schaik, Willem, LS IRAS EEPI GRA (Gezh.risico-analyse), Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA-SIB, de Been, Mark, Lanza, Val F., de Toro, María, Scharringa, Jelle, Dohmen, Wietske, Du, Yu, Hu, Juan, Lei, Ying, Li, Ning, Tooming-Klunderud, Ave, Heederik, Dick J J, Fluit, Ad C., Bonten, Marc J M, Willems, Rob J L, de la Cruz, Fernando, and van Schaik, Willem

Published
2014

45. Plasmid flux in escherichia coli ST131 sublineages, analyzed by plasmid constellation network (PLACNET), a new method for plasmid reconstruction from whole genome sequences

Author

Universidade de Santiago de Compostela. Departamento de Microbioloxía e Parasitoloxía, Lanza, Val F., de Toro, María, Garcillán Barcia, M., Mora Gutiérrez, Azucena, Blanco Álvarez, Jorge, Coque, Teresa M., Cruz, Fernando de la, Universidade de Santiago de Compostela. Departamento de Microbioloxía e Parasitoloxía, Lanza, Val F., de Toro, María, Garcillán Barcia, M., Mora Gutiérrez, Azucena, Blanco Álvarez, Jorge, Coque, Teresa M., and Cruz, Fernando de la

Abstract

Bacterial whole genome sequence (WGS) methods are rapidly overtaking classical sequence analysis. Many bacterial sequencing projects focus on mobilome changes, since macroevolutionary events, such as the acquisition or loss of mobile genetic elements, mainly plasmids, play essential roles in adaptive evolution. Existing WGS analysis protocols do not assort contigs between plasmids and the main chromosome, thus hampering full analysis of plasmid sequences. We developed a method (called plasmid constellation networks or PLACNET) that identifies, visualizes and analyzes plasmids in WGS projects by creating a network of contig interactions, thus allowing comprehensive plasmid analysis within WGS datasets. The workflow of the method is based on three types of data: assembly information (including scaffold links and coverage), comparison to reference sequences and plasmid-diagnostic sequence features. The resulting network is pruned by expert analysis, to eliminate confounding data, and implemented in a Cytoscape-based graphic representation. To demonstrate PLACNET sensitivity and efficacy, the plasmidome of the Escherichia coli lineage ST131 was analyzed. ST131 is a globally spread clonal group of extraintestinal pathogenic E. coli (ExPEC), comprising different sublineages with ability to acquire and spread antibiotic resistance and virulence genes via plasmids. Results show that plasmids flux in the evolution of this lineage, which is wide open for plasmid exchange. MOBF12/IncF plasmids were pervasive, adding just by themselves more than 350 protein families to the ST131 pangenome. Nearly 50% of the most frequent c–proteobacterial plasmid groups were found to be present in our limited sample of ten analyzed ST131 genomes, which represent the main ST131 sublineages

Published
2014

47. Dissemination of Cephalosporin Resistance Genes between Escherichia coli Strains from Farm Animals and Humans by Specific Plasmid Lineages

Author

de Been, Mark, primary, Lanza, Val F., additional, de Toro, María, additional, Scharringa, Jelle, additional, Dohmen, Wietske, additional, Du, Yu, additional, Hu, Juan, additional, Lei, Ying, additional, Li, Ning, additional, Tooming-Klunderud, Ave, additional, Heederik, Dick J. J., additional, Fluit, Ad C., additional, Bonten, Marc J. M., additional, Willems, Rob J. L., additional, de la Cruz, Fernando, additional, and van Schaik, Willem, additional

Published
2014
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48. Genome Analysis of Clostridium difficile PCR Ribotype 014 Lineage in Australian Pigs and Humans Reveals a Diverse Genetic Repertoire and Signatures of Long-Range Interspecies Transmission.

Author

Knight, Daniel R., Squire, Michele M., Collins, Deirdre A., Riley, Thomas V., Brukner, Ivan, and De Toro, María

Subjects
CLOSTRIDIOIDES difficile, VIRULENCE of bacteria, GENE expression in bacteria
Abstract

Clostridium difficile PCR ribotype (RT) 014 is well-established in both human and porcine populations in Australia, raising the possibility that C. difficile infection (CDI) may have a zoonotic or foodborne etiology. Here, whole genome sequencing and high-resolution core genome phylogenetics were performed on a contemporaneous collection of 40 Australian RT014 isolates of human and porcine origin. Phylogenies based on MLST (7 loci, STs 2, 13, and 49) and core orthologous genes (1260 loci) showed clustering of human and porcine strains indicative of very recent shared ancestry. Core genome single nucleotide variant (SNV) analysis found 42% of human strains showed a clonal relationship (separated by ≤2 SNVs in their core genome) with one or more porcine strains, consistent with recent inter-host transmission. Clones were spread over a vast geographic area with 50% of the human cases occurring without recent healthcare exposure. These findings suggest a persistent community reservoir with long-range dissemination, potentially due to agricultural recycling of piggery effluent. We also provide the first pan-genome analysis for this lineage, characterizing its resistome, prophage content, and in silico virulence potential. The RT014 is defined by a large "open" pan-genome (7587 genes) comprising a core genome of 2296 genes (30.3% of the total gene repertoire) and an accessory genome of 5291 genes. Antimicrobial resistance genotypes and phenotypes varied across host populations and ST lineages and were characterized by resistance to tetracycline [tetM, tetA(P), tetB(P) and tetW], clindamycin/erythromycin (ermB), and aminoglycosides (aph3-III-Sat4A-ant6-Ia). Resistance was mediated by clinically important mobile genetic elements, most notably Tn6194 (harboring ermB) and a novel variant of Tn5397 (harboring tetM). Numerous clinically important prophages (Siphoviridae and Myoviridae) were identified as well as an uncommon accessory gene regulator locus (agr3). Conservation in the pathogenicity locus and S-layer correlated with ST affiliation, further extending the concept of clonal C. difficile lineages. This study provides novel insights on the genetic variability and strain relatedness of C. difficile RT014, a lineage of emerging One Health importance. Ongoing molecular and genomic surveillance of strains in humans, animals, food, and the environment is imperative to identify opportunities to reduce the overall CDI burden. [ABSTRACT FROM AUTHOR]

Published
2017
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