Q3166793 (Q3166793): Difference between revisions
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(Changed an Item: Edited by the materialized bot - inferring region from the coordinates) |
(Created claim: summary (P836): ANTIBIOTIC-RESISTANT PATHOGENS, SUCH AS ENTEROCOCOCO-VANCOMYCIN-RESISTANT (REV) ARE A GROWING PROBLEM IN HOSPITALISED PATIENTS AND OFTEN CAUSE INFECTIONS AFTER ANTIBIOTIC TREATMENT. ERV INFECTIONS USUALLY START IN THE INTESTINE. UNDER NORMAL CONDITIONS, OUR INTESTINE IS COLONISED BY HUNDREDS OF COMMENSAL BACTERIA, THE MICROBIOTA, WHICH INHIBITS INTESTINAL COLONISATION BY VRE, WHICH IS CALLED “COLONISATION RESISTANCE” (CR). CONVERSELY, THE ADMINI...) |
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ANTIBIOTIC-RESISTANT PATHOGENS, SUCH AS ENTEROCOCOCO-VANCOMYCIN-RESISTANT (REV) ARE A GROWING PROBLEM IN HOSPITALISED PATIENTS AND OFTEN CAUSE INFECTIONS AFTER ANTIBIOTIC TREATMENT. ERV INFECTIONS USUALLY START IN THE INTESTINE. UNDER NORMAL CONDITIONS, OUR INTESTINE IS COLONISED BY HUNDREDS OF COMMENSAL BACTERIA, THE MICROBIOTA, WHICH INHIBITS INTESTINAL COLONISATION BY VRE, WHICH IS CALLED “COLONISATION RESISTANCE” (CR). CONVERSELY, THE ADMINISTRATION OF ANTIBIOTICS ALTERS THE COMPOSITION OF THE MICROBIOTA WHICH ALLOWS VRE TO COLONISE THE INTESTINE AND THEN SPREAD TO BLOOD WHERE IT CAN ENDANGER THE PATIENT’S LIFE. THEREFORE, UNDERSTANDING HOW AND WHAT MEMBERS OF THE MICROBIOTA CONFER CR AND HOW ANTIBIOTICS PROMOTE INFECTION IS CRUCIAL IF WE WANT TO PREVENT VRE INFECTIONS. HOWEVER, THE ABSENCE OF TECHNIQUES TO ANALYSE THE MICROBIOTA HAS MADE IT DIFFICULT TO STUDY THIS CLINICALLY RELEVANT FIELD. FORTUNATELY, NEW MASS SEQUENCING TECHNIQUES NOW ALLOW THE DETAILED STUDY OF THE MICROBIOTA AND ITS GENES (MICROBIOME). OUR GROUP HAS PIONEERED THIS NEW METHODOLOGY TO IDENTIFY MICROBIOTA CHANGES THAT PROMOTE VRE COLONISATION AND IDENTIFY THOSE BACTERIAL SPECIES THAT CONFER CR. WE HAVE SHOWN THAT THE REMOVAL OF CERTAIN BACTERIA FROM THE MICROBIOTA, INCLUDING BARNESIELLA, RUMINOCOCCACEAE, LACHNOSPIRACEAE, ALISTIPES, ALLOBACULUM, INCREASES THE RISK OF INFECTION. MOREOVER, THE RECONSTITUTION OF MICE TREATED WITH ANTIBIOTICS WITH THESE BACTERIA CONSIDERABLY DECREASES THE COLONISATION BY VRE. HAVING IDENTIFIED SPECIFIC MICROBIOTA BACTERIA THAT PROMOTE CR, IN THIS PROJECT WE PROPOSE TO IDENTIFY THE MECHANISMS BY WHICH THESE BACTERIA CONFER PROTECTION. OUR PUBLISHED RESULTS INDICATE THAT THE MICROBIOTA CONFERS CR IN THE ABSENCE OF ESSENTIAL COMPONENTS OF THE IMMUNE SYSTEM. THEREFORE, IN THIS PROJECT WE WILL FOCUS ON IDENTIFYING MECHANISMS BY WHICH THE MICROBIOTA DIRECTLY CONFERS RESISTANCE (COMPETICION BY NUTRIENTS, PRODUCTION OF INHIBITORY SUBSTANCES). TO ACHIEVE THIS GOAL, WE WILL FIRST DEFINE THE NUTRIENTS USED BY THE PATHOGEN AND PROTECTIVE BACTERIA (BPS) IN THE MICE INTESTINE. FOR THIS WE WILL USE OMIC TECHNIQUES (METAGENOMICA AND METATRANSCRIPTOMICA) TO IDENTIFY GENES EXPRESSED TO ACQUIRE IN VIVO NUTRIENTS, AND METABOLOMIC TECHNIQUES TO IDENTIFY NUTRIENTS THAT HAVE DECREASED IN VIVO AFTER COLONISATION BY VRE OR BPS. IN ADDITION, WE WILL IDENTIFY IN VITRO BY “ARRAYS” THE NUTRIENTS THAT ARE ESSENTIAL FOR THE GROWTH OF VRE, AND BY MEANS OF A TECHNIQUE OF IDENTIFICATION OF MUTANTS BY TRANSPOSITION IN VIVO, WE WILL IDENTIFY GENES THAT VRE NEEDS TO COLONISE THE INTESTINE AND ACQUIRE NUTRIENTS. ONCE THE STRATEGIES USED BY VRE AND BPS TO EXPLOIT NUTRIENTS HAVE BEEN DEFINED, IN VITRO AND IN VIVO COMPETICION TESTS WILL DEMONSTRATE THE ROLE OF NUTRIENT COMPETITION IN CR VERSUS VRE. ON THE OTHER HAND, THE IN VIVO OMIC PROFILES OF BPS WILL IDENTIFY POSSIBLE INHIBITOR MOLECULES THAT WILL BE TESTED IN GROWTH INHIBITION ASSAYS TO DEFINE THE ROLE OF THESE MOLECULES IN CR. THE INFORMATION OBTAINED IN THIS PROJECT WILL GIVE RISE TO NEW THERAPEUTIC STRATEGIES TO COMBAT ERV INFECTIONS, A PATHOGEN THAT IS ACQUIRING RESISTANCE TO THE FEW THERAPEUTIC OPTIONS AVAILABLE. (English) | |||||||||||||||
| Property / summary: ANTIBIOTIC-RESISTANT PATHOGENS, SUCH AS ENTEROCOCOCO-VANCOMYCIN-RESISTANT (REV) ARE A GROWING PROBLEM IN HOSPITALISED PATIENTS AND OFTEN CAUSE INFECTIONS AFTER ANTIBIOTIC TREATMENT. ERV INFECTIONS USUALLY START IN THE INTESTINE. UNDER NORMAL CONDITIONS, OUR INTESTINE IS COLONISED BY HUNDREDS OF COMMENSAL BACTERIA, THE MICROBIOTA, WHICH INHIBITS INTESTINAL COLONISATION BY VRE, WHICH IS CALLED “COLONISATION RESISTANCE” (CR). CONVERSELY, THE ADMINISTRATION OF ANTIBIOTICS ALTERS THE COMPOSITION OF THE MICROBIOTA WHICH ALLOWS VRE TO COLONISE THE INTESTINE AND THEN SPREAD TO BLOOD WHERE IT CAN ENDANGER THE PATIENT’S LIFE. THEREFORE, UNDERSTANDING HOW AND WHAT MEMBERS OF THE MICROBIOTA CONFER CR AND HOW ANTIBIOTICS PROMOTE INFECTION IS CRUCIAL IF WE WANT TO PREVENT VRE INFECTIONS. HOWEVER, THE ABSENCE OF TECHNIQUES TO ANALYSE THE MICROBIOTA HAS MADE IT DIFFICULT TO STUDY THIS CLINICALLY RELEVANT FIELD. FORTUNATELY, NEW MASS SEQUENCING TECHNIQUES NOW ALLOW THE DETAILED STUDY OF THE MICROBIOTA AND ITS GENES (MICROBIOME). OUR GROUP HAS PIONEERED THIS NEW METHODOLOGY TO IDENTIFY MICROBIOTA CHANGES THAT PROMOTE VRE COLONISATION AND IDENTIFY THOSE BACTERIAL SPECIES THAT CONFER CR. WE HAVE SHOWN THAT THE REMOVAL OF CERTAIN BACTERIA FROM THE MICROBIOTA, INCLUDING BARNESIELLA, RUMINOCOCCACEAE, LACHNOSPIRACEAE, ALISTIPES, ALLOBACULUM, INCREASES THE RISK OF INFECTION. MOREOVER, THE RECONSTITUTION OF MICE TREATED WITH ANTIBIOTICS WITH THESE BACTERIA CONSIDERABLY DECREASES THE COLONISATION BY VRE. HAVING IDENTIFIED SPECIFIC MICROBIOTA BACTERIA THAT PROMOTE CR, IN THIS PROJECT WE PROPOSE TO IDENTIFY THE MECHANISMS BY WHICH THESE BACTERIA CONFER PROTECTION. OUR PUBLISHED RESULTS INDICATE THAT THE MICROBIOTA CONFERS CR IN THE ABSENCE OF ESSENTIAL COMPONENTS OF THE IMMUNE SYSTEM. THEREFORE, IN THIS PROJECT WE WILL FOCUS ON IDENTIFYING MECHANISMS BY WHICH THE MICROBIOTA DIRECTLY CONFERS RESISTANCE (COMPETICION BY NUTRIENTS, PRODUCTION OF INHIBITORY SUBSTANCES). TO ACHIEVE THIS GOAL, WE WILL FIRST DEFINE THE NUTRIENTS USED BY THE PATHOGEN AND PROTECTIVE BACTERIA (BPS) IN THE MICE INTESTINE. FOR THIS WE WILL USE OMIC TECHNIQUES (METAGENOMICA AND METATRANSCRIPTOMICA) TO IDENTIFY GENES EXPRESSED TO ACQUIRE IN VIVO NUTRIENTS, AND METABOLOMIC TECHNIQUES TO IDENTIFY NUTRIENTS THAT HAVE DECREASED IN VIVO AFTER COLONISATION BY VRE OR BPS. IN ADDITION, WE WILL IDENTIFY IN VITRO BY “ARRAYS” THE NUTRIENTS THAT ARE ESSENTIAL FOR THE GROWTH OF VRE, AND BY MEANS OF A TECHNIQUE OF IDENTIFICATION OF MUTANTS BY TRANSPOSITION IN VIVO, WE WILL IDENTIFY GENES THAT VRE NEEDS TO COLONISE THE INTESTINE AND ACQUIRE NUTRIENTS. ONCE THE STRATEGIES USED BY VRE AND BPS TO EXPLOIT NUTRIENTS HAVE BEEN DEFINED, IN VITRO AND IN VIVO COMPETICION TESTS WILL DEMONSTRATE THE ROLE OF NUTRIENT COMPETITION IN CR VERSUS VRE. ON THE OTHER HAND, THE IN VIVO OMIC PROFILES OF BPS WILL IDENTIFY POSSIBLE INHIBITOR MOLECULES THAT WILL BE TESTED IN GROWTH INHIBITION ASSAYS TO DEFINE THE ROLE OF THESE MOLECULES IN CR. THE INFORMATION OBTAINED IN THIS PROJECT WILL GIVE RISE TO NEW THERAPEUTIC STRATEGIES TO COMBAT ERV INFECTIONS, A PATHOGEN THAT IS ACQUIRING RESISTANCE TO THE FEW THERAPEUTIC OPTIONS AVAILABLE. (English) / rank | |||||||||||||||
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| Property / summary: ANTIBIOTIC-RESISTANT PATHOGENS, SUCH AS ENTEROCOCOCO-VANCOMYCIN-RESISTANT (REV) ARE A GROWING PROBLEM IN HOSPITALISED PATIENTS AND OFTEN CAUSE INFECTIONS AFTER ANTIBIOTIC TREATMENT. ERV INFECTIONS USUALLY START IN THE INTESTINE. UNDER NORMAL CONDITIONS, OUR INTESTINE IS COLONISED BY HUNDREDS OF COMMENSAL BACTERIA, THE MICROBIOTA, WHICH INHIBITS INTESTINAL COLONISATION BY VRE, WHICH IS CALLED “COLONISATION RESISTANCE” (CR). CONVERSELY, THE ADMINISTRATION OF ANTIBIOTICS ALTERS THE COMPOSITION OF THE MICROBIOTA WHICH ALLOWS VRE TO COLONISE THE INTESTINE AND THEN SPREAD TO BLOOD WHERE IT CAN ENDANGER THE PATIENT’S LIFE. THEREFORE, UNDERSTANDING HOW AND WHAT MEMBERS OF THE MICROBIOTA CONFER CR AND HOW ANTIBIOTICS PROMOTE INFECTION IS CRUCIAL IF WE WANT TO PREVENT VRE INFECTIONS. HOWEVER, THE ABSENCE OF TECHNIQUES TO ANALYSE THE MICROBIOTA HAS MADE IT DIFFICULT TO STUDY THIS CLINICALLY RELEVANT FIELD. FORTUNATELY, NEW MASS SEQUENCING TECHNIQUES NOW ALLOW THE DETAILED STUDY OF THE MICROBIOTA AND ITS GENES (MICROBIOME). OUR GROUP HAS PIONEERED THIS NEW METHODOLOGY TO IDENTIFY MICROBIOTA CHANGES THAT PROMOTE VRE COLONISATION AND IDENTIFY THOSE BACTERIAL SPECIES THAT CONFER CR. WE HAVE SHOWN THAT THE REMOVAL OF CERTAIN BACTERIA FROM THE MICROBIOTA, INCLUDING BARNESIELLA, RUMINOCOCCACEAE, LACHNOSPIRACEAE, ALISTIPES, ALLOBACULUM, INCREASES THE RISK OF INFECTION. MOREOVER, THE RECONSTITUTION OF MICE TREATED WITH ANTIBIOTICS WITH THESE BACTERIA CONSIDERABLY DECREASES THE COLONISATION BY VRE. HAVING IDENTIFIED SPECIFIC MICROBIOTA BACTERIA THAT PROMOTE CR, IN THIS PROJECT WE PROPOSE TO IDENTIFY THE MECHANISMS BY WHICH THESE BACTERIA CONFER PROTECTION. OUR PUBLISHED RESULTS INDICATE THAT THE MICROBIOTA CONFERS CR IN THE ABSENCE OF ESSENTIAL COMPONENTS OF THE IMMUNE SYSTEM. THEREFORE, IN THIS PROJECT WE WILL FOCUS ON IDENTIFYING MECHANISMS BY WHICH THE MICROBIOTA DIRECTLY CONFERS RESISTANCE (COMPETICION BY NUTRIENTS, PRODUCTION OF INHIBITORY SUBSTANCES). TO ACHIEVE THIS GOAL, WE WILL FIRST DEFINE THE NUTRIENTS USED BY THE PATHOGEN AND PROTECTIVE BACTERIA (BPS) IN THE MICE INTESTINE. FOR THIS WE WILL USE OMIC TECHNIQUES (METAGENOMICA AND METATRANSCRIPTOMICA) TO IDENTIFY GENES EXPRESSED TO ACQUIRE IN VIVO NUTRIENTS, AND METABOLOMIC TECHNIQUES TO IDENTIFY NUTRIENTS THAT HAVE DECREASED IN VIVO AFTER COLONISATION BY VRE OR BPS. IN ADDITION, WE WILL IDENTIFY IN VITRO BY “ARRAYS” THE NUTRIENTS THAT ARE ESSENTIAL FOR THE GROWTH OF VRE, AND BY MEANS OF A TECHNIQUE OF IDENTIFICATION OF MUTANTS BY TRANSPOSITION IN VIVO, WE WILL IDENTIFY GENES THAT VRE NEEDS TO COLONISE THE INTESTINE AND ACQUIRE NUTRIENTS. ONCE THE STRATEGIES USED BY VRE AND BPS TO EXPLOIT NUTRIENTS HAVE BEEN DEFINED, IN VITRO AND IN VIVO COMPETICION TESTS WILL DEMONSTRATE THE ROLE OF NUTRIENT COMPETITION IN CR VERSUS VRE. ON THE OTHER HAND, THE IN VIVO OMIC PROFILES OF BPS WILL IDENTIFY POSSIBLE INHIBITOR MOLECULES THAT WILL BE TESTED IN GROWTH INHIBITION ASSAYS TO DEFINE THE ROLE OF THESE MOLECULES IN CR. THE INFORMATION OBTAINED IN THIS PROJECT WILL GIVE RISE TO NEW THERAPEUTIC STRATEGIES TO COMBAT ERV INFECTIONS, A PATHOGEN THAT IS ACQUIRING RESISTANCE TO THE FEW THERAPEUTIC OPTIONS AVAILABLE. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 18:05, 12 October 2021
Project Q3166793 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3166793 in Spain |
Statements
96,800.0 Euro
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193,600.0 Euro
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50.0 percent
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1 January 2015
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30 June 2018
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FUNDACION PARA EL FOMENTO DE LA INV. SANITARIA Y BIOMEDICA DE LA COMUNIDAD VALENCIANA (FISABIO)
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39°28'10.96"N, 0°22'34.82"W
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46250
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PATOGENOS RESISTENTES A ANTIBIOTICOS, TALES COMO EL ENTEROCOCO-VANCOMICINA-RESISTENTE (VRE) SON UN PROBLEMA CRECIENTE EN PACIENTES HOSPITALIZADOS Y SUELEN CAUSAR INFECCIONES TRAS EL TRATAMIENTO ANTIBIOTICO. INFECCIONES POR VRE SUELEN COMENZAR EN EL INTESTINO. EN CONDICIONES NORMALES, NUESTRO INTESTINO ESTA COLONIZADO POR CIENTOS DE BACTERIAS COMENSALES, LA MICROBIOTA, QUE INHIBE LA COLONIZACION INTESTINAL POR VRE, LO QUE SE DENOMINA "RESISTENCIA A LA COLONIZACION" (CR). POR CONTRA, LA ADMINISTRACION DE ANTIBIOTICOS ALTERA LA COMPOSICION DE LA MICROBIOTA LO QUE PERMITE A VRE COLONIZAR EL INTESTINO Y POSTERIORMENTE DISEMINAR A SANGRE DONDE PUEDE PONER EN PELIGRO LA VIDA DEL PACIENTE. POR TANTO, ENTENDER COMO Y QUE MIEMBROS DE LA MICROBIOTA CONFIEREN CR Y COMO LOS ANTIBIOTICOS PROMUEVEN LA INFECCION ES CRUCIAL SI QUEREMOS PREVENIR LAS INFECCIONES POR VRE. SIN EMBARGO, LA AUSENCIA DE TECNICAS PARA ANALIZAR LA MICROBIOTA HA DIFICULTADO EL ESTUDIO DE ESTE CLINICAMENTE RELEVANTE CAMPO. AFORTUNADAMENTE, NUEVAS TECNICAS DE SECUENCIACION MASIVA PERMITEN AHORA EL ESTUDIO DETALLADO DE LA MICROBIOTA Y SUS GENES (MICROBIOMA). NUESTRO GRUPO HA SIDO PIONERO EN APLICAR ESTA NUEVA METODOLOGIA PARA IDENTIFICAR CAMBIOS EN LA MICROBIOTA QUE PROMUEVEN LA COLONIZACION POR VRE E IDENTIFICAR AQUELLAS ESPECIES BACTERIANAS QUE CONFIEREN CR. HEMOS DEMOSTRADO QUE LA ELIMINACION DE CIERTAS BACTERIAS DE LA MICROBIOTA, INCLUIDAS BARNESIELLA, RUMINOCOCCACEAE, LACHNOSPIRACEAE, ALISTIPES, ALLOBACULUM, INCREMENTA EL RIESGO DE INFECCION. MAS AUN, LA RECONSTITUCION DE RATONES TRATADOS CON ANTIBIOTICOS CON DICHAS BACTERIAS DISMINUYE CONSIDERABLEMENTE LA COLONIZACION POR VRE. HABIENDO IDENTIFICADO BACTERIAS CONCRETAS DE LA MICROBIOTA QUE PROMUEVEN CR, EN ESTE PROYECTO PROPONEMOS IDENTIFICAR LOS MECANISMOS POR LOS CUALES DICHAS BACTERIAS CONFIEREN PROTECCION. NUESTROS RESULTADOS PUBLICADOS INDICAN QUE LA MICROBIOTA CONFIERE CR EN AUSENCIA DE COMPONENTES ESENCIALES DEL SISTEMA INMUNE. POR ELLO, EN ESTE PROYECTO NOS CENTRAREMOS EN IDENTIFICAR MECANISMOS POR LOS CUALES LA MICROBIOTA DIRECTAMENTE CONFIERE RESISTENCIA (COMPETICION POR NUTRIENTES, PRODUCCION DE SUSTANCIAS INHIBITORIAS). PARA ALCANZAR ESTE OBJETIVO, PRIMERO DEFINIREMOS LOS NUTRIENTES UTILIZADOS POR EL PATOGENO Y LAS BACTERIAS PROTECTORAS (BPS) EN EL INTESTINO DE RATONES. PARA ELLO UTILIZAREMOS TECNICAS OMICAS (METAGENOMICA Y METATRANSCRIPTOMICA) PARA IDENTIFICAR LOS GENES EXPRESADOS PARA ADQUIRIR NUTRIENTES IN VIVO, Y TECNICAS METABOLOMICAS PARA IDENTIFICAR NUTRIENTES QUE HAYAN MERMADO IN VIVO TRAS LA COLONIZACION POR VRE O BPS. ADEMAS, IDENTIFICAREMOS IN VITRO MEDIANTE "ARRAYS" LOS NUTRIENTES QUE SON ESENCIALES PARA EL CRECIMIENTO DE VRE, Y MEDIANTE UNA TECNICA DE IDENTIFICACION DE MUTANTES POR TRANSPOSICION IN VIVO, IDENTIFICAREMOS GENES QUE NECESITA VRE PARA COLONIZAR EL INTESTINO Y ADQUIRIR NUTRIENTES. UNA VEZ DEFINIDAS LAS ESTRATEGIAS UTILIZADAS POR VRE Y BPS PARA EXPLOTAR NUTRIENTES, ENSAYOS DE COMPETICION IN VITRO E IN VIVO DEMOSTRARAN EL PAPEL DE LA COMPETICION POR NUTRIENTES EN CR FRENTE A VRE. POR OTRO LADO, LOS PERFILES OMICOS IN VIVO DE LAS BPS IDENTIFICARAN POSIBLES MOLECULAS INHIBIDORAS QUE SERAN TESTADAS EN ENSAYOS DE INHIBICION DE CRECIMIENTO PARA DEFINIR EL PAPEL DE ESTAS MOLECULAS EN CR. LA INFORMACION OBTENIDA EN ESTE PROYECTO DARA LUGAR A NUEVAS ESTRATEGIAS TERAPEUTICAS PARA COMBATIR INFECCIONES POR VRE, UN PATOGENO QUE ESTA ADQUIRIENDO RESISTENCIAS A LAS POCAS OPCIONES TERAPEUTICAS DISPONIBLES. (Spanish)
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ANTIBIOTIC-RESISTANT PATHOGENS, SUCH AS ENTEROCOCOCO-VANCOMYCIN-RESISTANT (REV) ARE A GROWING PROBLEM IN HOSPITALISED PATIENTS AND OFTEN CAUSE INFECTIONS AFTER ANTIBIOTIC TREATMENT. ERV INFECTIONS USUALLY START IN THE INTESTINE. UNDER NORMAL CONDITIONS, OUR INTESTINE IS COLONISED BY HUNDREDS OF COMMENSAL BACTERIA, THE MICROBIOTA, WHICH INHIBITS INTESTINAL COLONISATION BY VRE, WHICH IS CALLED “COLONISATION RESISTANCE” (CR). CONVERSELY, THE ADMINISTRATION OF ANTIBIOTICS ALTERS THE COMPOSITION OF THE MICROBIOTA WHICH ALLOWS VRE TO COLONISE THE INTESTINE AND THEN SPREAD TO BLOOD WHERE IT CAN ENDANGER THE PATIENT’S LIFE. THEREFORE, UNDERSTANDING HOW AND WHAT MEMBERS OF THE MICROBIOTA CONFER CR AND HOW ANTIBIOTICS PROMOTE INFECTION IS CRUCIAL IF WE WANT TO PREVENT VRE INFECTIONS. HOWEVER, THE ABSENCE OF TECHNIQUES TO ANALYSE THE MICROBIOTA HAS MADE IT DIFFICULT TO STUDY THIS CLINICALLY RELEVANT FIELD. FORTUNATELY, NEW MASS SEQUENCING TECHNIQUES NOW ALLOW THE DETAILED STUDY OF THE MICROBIOTA AND ITS GENES (MICROBIOME). OUR GROUP HAS PIONEERED THIS NEW METHODOLOGY TO IDENTIFY MICROBIOTA CHANGES THAT PROMOTE VRE COLONISATION AND IDENTIFY THOSE BACTERIAL SPECIES THAT CONFER CR. WE HAVE SHOWN THAT THE REMOVAL OF CERTAIN BACTERIA FROM THE MICROBIOTA, INCLUDING BARNESIELLA, RUMINOCOCCACEAE, LACHNOSPIRACEAE, ALISTIPES, ALLOBACULUM, INCREASES THE RISK OF INFECTION. MOREOVER, THE RECONSTITUTION OF MICE TREATED WITH ANTIBIOTICS WITH THESE BACTERIA CONSIDERABLY DECREASES THE COLONISATION BY VRE. HAVING IDENTIFIED SPECIFIC MICROBIOTA BACTERIA THAT PROMOTE CR, IN THIS PROJECT WE PROPOSE TO IDENTIFY THE MECHANISMS BY WHICH THESE BACTERIA CONFER PROTECTION. OUR PUBLISHED RESULTS INDICATE THAT THE MICROBIOTA CONFERS CR IN THE ABSENCE OF ESSENTIAL COMPONENTS OF THE IMMUNE SYSTEM. THEREFORE, IN THIS PROJECT WE WILL FOCUS ON IDENTIFYING MECHANISMS BY WHICH THE MICROBIOTA DIRECTLY CONFERS RESISTANCE (COMPETICION BY NUTRIENTS, PRODUCTION OF INHIBITORY SUBSTANCES). TO ACHIEVE THIS GOAL, WE WILL FIRST DEFINE THE NUTRIENTS USED BY THE PATHOGEN AND PROTECTIVE BACTERIA (BPS) IN THE MICE INTESTINE. FOR THIS WE WILL USE OMIC TECHNIQUES (METAGENOMICA AND METATRANSCRIPTOMICA) TO IDENTIFY GENES EXPRESSED TO ACQUIRE IN VIVO NUTRIENTS, AND METABOLOMIC TECHNIQUES TO IDENTIFY NUTRIENTS THAT HAVE DECREASED IN VIVO AFTER COLONISATION BY VRE OR BPS. IN ADDITION, WE WILL IDENTIFY IN VITRO BY “ARRAYS” THE NUTRIENTS THAT ARE ESSENTIAL FOR THE GROWTH OF VRE, AND BY MEANS OF A TECHNIQUE OF IDENTIFICATION OF MUTANTS BY TRANSPOSITION IN VIVO, WE WILL IDENTIFY GENES THAT VRE NEEDS TO COLONISE THE INTESTINE AND ACQUIRE NUTRIENTS. ONCE THE STRATEGIES USED BY VRE AND BPS TO EXPLOIT NUTRIENTS HAVE BEEN DEFINED, IN VITRO AND IN VIVO COMPETICION TESTS WILL DEMONSTRATE THE ROLE OF NUTRIENT COMPETITION IN CR VERSUS VRE. ON THE OTHER HAND, THE IN VIVO OMIC PROFILES OF BPS WILL IDENTIFY POSSIBLE INHIBITOR MOLECULES THAT WILL BE TESTED IN GROWTH INHIBITION ASSAYS TO DEFINE THE ROLE OF THESE MOLECULES IN CR. THE INFORMATION OBTAINED IN THIS PROJECT WILL GIVE RISE TO NEW THERAPEUTIC STRATEGIES TO COMBAT ERV INFECTIONS, A PATHOGEN THAT IS ACQUIRING RESISTANCE TO THE FEW THERAPEUTIC OPTIONS AVAILABLE. (English)
12 October 2021
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Valencia
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Identifiers
SAF2014-60234-R
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