Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"

Tesis doctoral inédita leída en la Universidad Aautónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 23-05-2015

Detalles Bibliográficos
Autor: Aguilera Rossi, Cristian Gustavo
Tipo de recurso: tesis doctoral
Fecha de publicación:2015
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:español
OAI Identifier:oai:repositorio.uam.es:10486/667537
Acceso en línea:http://hdl.handle.net/10486/667537
Access Level:acceso abierto
Palabra clave:Pseudomonas - Tesis doctorales
Biología y Biomedicina / Biología
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dc.title.none.fl_str_mv Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
title Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
spellingShingle Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
Aguilera Rossi, Cristian Gustavo
Pseudomonas - Tesis doctorales
Biología y Biomedicina / Biología
title_short Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
title_full Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
title_fullStr Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
title_full_unstemmed Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
title_sort Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"
dc.creator.none.fl_str_mv Aguilera Rossi, Cristian Gustavo
author Aguilera Rossi, Cristian Gustavo
author_facet Aguilera Rossi, Cristian Gustavo
author_role author
dc.contributor.none.fl_str_mv Ayala Serrano, Juan Alfonso
Departamento de Biología Molecular
Facultad de Ciencias
Centro de Biología Molecular Severo Ochoa (CBM)
dc.subject.none.fl_str_mv Pseudomonas - Tesis doctorales
Biología y Biomedicina / Biología
topic Pseudomonas - Tesis doctorales
Biología y Biomedicina / Biología
description Tesis doctoral inédita leída en la Universidad Aautónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 23-05-2015
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-05-23
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/667537
url http://hdl.handle.net/10486/667537
dc.language.none.fl_str_mv Español
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language_invalid_str_mv Español
language spa
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
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spelling Caracterización funcional y estructural de LMM-PBP4 y análisis de su papel moderador en la integridad molecular del peptidoglicano para el modelo bacteriano "Pseudomonas aeroginosa"Aguilera Rossi, Cristian GustavoPseudomonas - Tesis doctoralesBiología y Biomedicina / BiologíaTesis doctoral inédita leída en la Universidad Aautónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 23-05-2015Nosocomial and community-acquired infections by Pseudomonas aeruginosa continue to represent a major therapeutic challenge where the choice of an appropriate antibiotic is essential. Resistance of this pathogen against β-lactam antibiotics is mainly determined by the production of inactivating enzymes (β-lactamases) AmpC type whose regulatory mechanism is much more complex than the existing in members of the Enterobacteriaceae family, by including the protein AmpR responsible for regulation of additional genes in regards to ampC, such as ampE and creD as well as dacB, involved in the overproduction of this cephalosporinase. The connection between the replacement and recycling processes of peptidoglycan and its regulatory pathways for constitutive overproduction of chromosomal AmpC β-lactamase, particularly the mechanism associated with inactivation of PBP4, raises a need for detailed structural and functional research of this LMM-PBP class C subclass C1 in Pseudomonas aeruginosa that allows to establish similarities and differences with other low molecular mass penicillin-binding proteins in this bacterial model and between functional orthologs from related species, also evaluating its participation in the metabolism of cell wall and the biology of resistance to β-lactam antibiotics. The methodological approach designed and implemented to address this Thesis demonstrated the lack of β-lactamase activity for the LMM-PBP4 native form, the presence of DD-carboxypeptidase and DD-endopeptidase activities in this protein (this last was defined as the predominant activity) and its absence at the site of cell division discarding its association with septal and bacterial divisome proteins. Its subcellular localization in the inner membrane and periplasmic space strengthens its proposal as a potential hydrolase-autolysin associated with the maturationrecycling of the peptidoglycan. The high affinity demonstrated between the β-lactam antibiotics cefoxitin and imipenem with LMM-PBP4 (purified and bound to membrane) correlates with the binding activity for these proteins and their probable inactivation and its role on constitutive overproduction of AmpC β-lactamase. The structural model for the monomeric unit of LMM-PBP4 confirms the presence of domains II and III which define it as a LMM-PBP class C subclass C1 allowing to estimate the dimension of the cavity in the active site that favors the access of large substrates and recognizes the existence of a threonine amino acid at position 386 (T386) which would accommodate the peptide chain of a second strand of peptidoglycan. These structural precedents support the development of a DD-endopeptidase activity in this protein. Analysis of the cell wall in relation to its muropeptides composition from the reference strain and mutants in regulatory proteins for AmpC production (DacB, AmpE, AmpDh2) under natural conditions, supplementationoverexpression and antibiotic inactivation of LMM-PBP4, exhibits no changes to propose an activation system for ampC via an effector of pentapeptide nature but confirms in vivo the DD-peptidase bifunctionality mentioned above. Moreover, it was achieved the identification of new muropeptides related to structure and functionality still not described in Pseudomonas aeruginosaAyala Serrano, Juan AlfonsoDepartamento de Biología MolecularFacultad de CienciasCentro de Biología Molecular Severo Ochoa (CBM)20152015-05-23doctoral thesishttp://purl.org/coar/resource_type/c_db06NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10486/667537reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridEspañolspaopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6675372026-06-23T12:46:27Z
score 15,300719

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