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dc.date.available
2023-01-10T15:38:06Z
dc.identifier.citation
Llarrull, Leticia Irene; Testero, Sebastian Andres; (2023): Sintesis de fotosondas derivadas de ampicilina. Consejo Nacional de Investigaciones Científicas y Técnicas. (dataset). http://hdl.handle.net/11336/184179
dc.identifier.uri
http://hdl.handle.net/11336/184179
dc.description.abstract
The Gram-positive bacteria Staphylococcus aureus is the main cause of hospital- and community-associated infections. S. aureus is the most frequent cause of surgical, lower respiratory tract, and cardiovascular infections. In addition, it is the second most common cause of health-care associated pneumonia and of bloodstream infections.1,2,5 Methicillin-resistant S. aureus (MRSA) is a high priority concern in the world and in particular in Latin America, both in hospitals and in the community. MRSA has become the first cause of hospital-associated infections in Latin America, and there has been an increasing number of reports of community acquired MRSA infections. The acquisition of resistance to b-lactam antibiotics, generally concurrent with the acquisition of resistance to other antibacterial agents, represents a huge challenge for the prevention and treatment of S. aureus associated infections. Very few new antibacterial are in advanced stages of clinical evaluation for the treatment of bacterial infections, including MRSA. S. aureus presents two main mechanisms of resistance to b-lactam antibiotics: the expression of the PC1 b-lactamase, capable of hydrolyzing and inactivating the b-lactam antibiotics, and the acquisition of a PBP (PBP2a) with low affinity for b-lactam antibiotics, and which is hence not inhibited by them. S. aureus presents another important system that coordinates the response to antibiotics that inhibit the biosynthesis of the peptidoglycan: the VraSRT system. The three-component system VraSRT controls the peptidoglycan crosslinking process, and is activated by β-lactam and glycopeptide antibiotics. VraSRT has a critical role in glycopeptide-resistance. The VraSRT system is composed of three components: VraS and VraT are membrane proteins that could quickly detect stress in the cell wall and transmit the signal to the cell cytoplasm. The understanding of the signal transduction mechanism employed by the sensor proteins of the VraSRT system is of great interest because they are possible targets for the design of inhibitors that can be used in conjunction with antibiotics for the treatment of S. aureus infections. Photoaffinity labeling is a useful technique employed to study noncovalent interactions between protein-ligands and protein-protein complexes. A photoaffinity labeling reagent is a molecule that contains a photoreactive group which produces highly reactive intermediates upon photolysis. The most widely used classes of photoactive functionality include benzophenones, trifluoromethylphenyldiazirines, and arylazides, which give rise to diradicals, carbenes and nitrenes by UV irradiation. These generated intermediates can produce hydrogen abstraction reactions, initiate highly efficiency double bond addition reactions, insertion reactions to C-H and N-H bonds (carbenes, nitrenes) with neighboring biomolecules giving stable covalent adducts. Each of these families of compounds have advantages and disadvantages. For example, benzophenones are chemically more stable than azides and diazirines, can be manipulated in ambient light and like diazirines are activated at 350 nm avoiding wavelengths that cause protein damage. However, its bulky size and hydrophobicity can complicate the binding with the macromolecule. On the other hand, arylazides give reactions with high efficiency, present excellent stability for storage and their synthesis is easy but they are activated at wavelengths that could affect the biological system under study. Finally, trifluoromethylphenyldiazirines meet most of the characteristics of an ideal photoreactive, although their synthesis needs more steps. Herein, we report the synthesis of modified variants of β-lactam antibiotics that can be used as affinity photoprobes in order to elucidate the molecular events that lead to the induction of resistance systems in bacteria. Using these photoprobes we demonstrate that the membrane protein VraS interacts directly with β-lactam antibiotics, which results in its autophosphorylation and phosphotransfer to VraR.
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.title
Sintesis de fotosondas derivadas de ampicilina
dc.type
dataset
dc.date.updated
2022-07-19T14:10:19Z
dc.description.fil
Fil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil
Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
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dc.datacite.PublicationYear
2023
dc.datacite.Creator
Llarrull, Leticia Irene
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dc.datacite.Creator
Testero, Sebastian Andres
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dc.datacite.affiliation
Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario
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dc.datacite.affiliation
Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario
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dc.datacite.publisher
Consejo Nacional de Investigaciones Científicas y Técnicas
dc.datacite.subject
Química Orgánica
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dc.datacite.subject
Ciencias Químicas
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dc.datacite.subject
CIENCIAS NATURALES Y EXACTAS
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dc.datacite.date
03/2015-05/2017
dc.datacite.DateType
Creado
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dc.datacite.language
eng
dc.datacite.version
1.0
dc.datacite.description
Parte experimental
dc.datacite.DescriptionType
Métodos
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dc.datacite.FundingReference
PICT-2013-0505
dc.datacite.FundingReference
PICT-2015-2521
dc.datacite.FunderName
Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica. Fondo para la Investigación Científica y Tecnológica
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dc.datacite.FunderName
Ministerio de Ciencia, Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica. Fondo para la Investigación Científica y Tecnológica
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dc.subject.keyword
AMPICILINA
dc.subject.keyword
FOTOSONDA
dc.subject.keyword
STAPHYLOCOCCUS AUREUS
dc.datacite.resourceTypeGeneral
dataset
dc.conicet.datoinvestigacionid
1780
dc.datacite.awardTitle
Elucidación de los eventos moleculares que dan lugar a la manifestación de resistencia en Staphylococcus aureus mediante el uso de fotosondas
dc.datacite.awardTitle
Caracterización estructural y funcional de las proteínas sensoras de los sistemas de resistencia a beta-lactámicos de Staphylococcusaureus
dc.datacite.geolocation
Rosario
dc.datacite.formatedDate
2015-2017
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