BIOLOGIA MOLECULAR DE ISLAS DE PATOGENICIDAD DE STAPHYLOCOCCUS AUREUS
STAPHYLOCOCCUS AUREUS IS A HAZARDOUS PATHOGEN BOTH FOR HUMANS AND ANIMALS DUE TO THE ENORMOUS VARIETY OF INFECTIONS IT PRODUCES AND THE EMERGENCE OF MULTIDRUG-RESISTANT STRAINS, S, AUREUS IS THE MOST COMMON CAUSE OF SKIN INFECTION...
STAPHYLOCOCCUS AUREUS IS A HAZARDOUS PATHOGEN BOTH FOR HUMANS AND ANIMALS DUE TO THE ENORMOUS VARIETY OF INFECTIONS IT PRODUCES AND THE EMERGENCE OF MULTIDRUG-RESISTANT STRAINS, S, AUREUS IS THE MOST COMMON CAUSE OF SKIN INFECTIONS AND ONCE IT PENETRATES THE SUBCUTANEOUS TISSUES AND REACHES THE BLOOD IT CAN INFECT ALMOST ANY ORGAN, THE ENORMOUS PATHOGENIC EFFICIENCY OF S, AUREUS RELIES ON ITS CAPACITY TO PERSIST AND MULTIPLY IN DIFFERENT ENVIRONMENTS AS WELL AS ON ITS CAPACITY TO PRODUCE A LARGE VARIETY OF TOXINS, MOST OF WHICH ARE ENCODED IN MOBILE PATHOGENICITY ISLANDS, WE HYPOTHESIZE THAT BOTH ADAPTATION TO DIFFERENT ENVIRONMENTS AND MOBILITY-DISSEMINATION OF PATHOGENICITY ISLANDS HARBOURING TOXIN GENES ARE REGULATED BY THE BACTERIAL SENSORIAL SYSTEM, S, AUREUS AND BACTERIA IN GENERAL HAVE DEVELOPED SIGNAL TRANSDUCTION SYSTEMS TO TRANSMIT THE STIMULI TO THE CELLULAR MACHINERY, A KEY ELEMENT OF THE BACTERIAL SENSORIAL SYSTEMS IS THE TWO-COMPONENT PHOSPHORELAY SYSTEM (TCS) THAT CONSISTS OF A MEMBRANE BOUND SENSOR, WHICH RESPONDS TO AN EXTRACELLULAR SIGNAL BY PHOSPHORYLATING A CYTOSOLIC RESPONSE REGULATOR, ALTHOUGH MANY BACTERIA CONTAIN VARIOUS DOZENS OF TCS, CLASSICAL GENETIC STRATEGIES HAVE INFERRED THE FUNCTION OF TCS FROM THE PHENOTYPES DISPLAYED BY MUTANTS IN SINGLE TCS, WITHOUT CONSIDERING THAT THE REMANT MEMBERS OF THE FAMILY MIGHT EXERT COMPENSATORY OR INTERFERING EFFECTS, THUS, IN THIS COORDINATED PROJECT, SUBPROJECT 1 PROPOSES A GLOBAL STRATEGY TO ANALYZE THE TCS SENSORIAL SYSTEM BASED ON THE ANALYSIS OF A RECOMBINANT STRAIN IN WHICH ALL THE NON-ESSENTIAL TCS (FIFTEEN) PRESENT IN THE GENOME OF S, AUREUS WILL BE DELETED, THEN, USING THE REVERSE PROCESS, A COLLECTION OF DERIVATIVES OF THE MUTANT STRAIN CONTAINING A CHROMOSOMAL COPY OF EACH TCS WILL BE GENERATED, THE ANALYSIS OF THIS COLLECTION OF STRAINS WILL ALLOW US TO DETERMINE THE EXTENT OF BIOLOGICAL PROCESS AFFECTED BY TCS SENSORIAL SYSTEM, PAYING SPECIAL ATTENTION TO BIOFILM FORMATION, INTERACTION WITH HOST CELLS AND VIRULENCE,SUBPROJECT 2 IS DEVOTED TO THE MOLECULAR CHARACTERIZATION OF THE MOBILITY-DISSEMINATION CYCLE OF PATHOGENICITY ISLANDS OF S, AUREUS, PATHOGENICITY ISLANDS ARE LARGELY RESPONSIBLE FOR THE WIDE VARIETY OF ADAPTATIONS TO LIFE IN DIFFERENT ENVIRONMENTS, HOST TISSUES AND ANTIBIOTIC RESISTANCE, ITS MOBILITY IS A HIGHLY REGULATED PROCESS THAT DEPENDS ON PARTICULAR ENVIRONMENTAL CONDITIONS, INITIALLY, SUBPROJECT 2 WILL ANALYZE THE ELEMENTS INVOLVED IN THE EXCISION-REPLICATION-PACKAGING OF S, AUREUS PATHOGENICITY ISLANDS AND AFTERWARDS THIS SUBPROJECT WILL EXPLOIT THE COLLECTION OF MUTANT STRAINS CONTAINING SINGLE TCS OR DEFICIENT IN TCS TO EVALUATE THE ROLE OF TCS IN THE REGULATION OF THE MOBILITY OF PATHOGENICITY ISLANDS AND THE PRODUCTION OF TOXINS ENCODED BY THEM IN RESPONSE TO ENVIRONMENTAL SIGNALS,KEEPING IN MIND THAT TCS DO NOT EXIST IN HUMANS, THE RESULTS OF THIS PROJECT MIGHT BE USEFUL TO EVALUATE THE POTENTIAL OF TCS AS NEW TARGETS FOR DEVELOPING OF ANTIMICROBIALS AND/OR INHIBITORS THAT PREVENTED DISSEMINATION OF VIRULENCE FACTORS ENCODED IN MOBILE ELEMENTS, Staphylococcus aureus\sistemas sensoriales\sistemas de dos-componentes\islas de patogenicidad\fagos\biofilm\virulencia\transferencia horizontal de genesver más
17-09-2024:
HORIZON-CL5-2024-D4-02-05
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