Banca de DEFESA: BRUNO AMORIM DO CARMO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : BRUNO AMORIM DO CARMO
DATE: 14/12/2023
TIME: 14:00
LOCAL: Videoconferencia - Link para acesso: https://meet.google.com/jem-wkyu-mgc
TITLE:

 

IN VITRO AND IN VIVO ACTIVITY OF ANTIMICROBIAL PEP-TIDESANALOGSINCORPORATEDINTOPLGANANOPARTICLES

 

AGAINSTStaphylococcusaureus

KEY WORDS:

 

Tityus stigmurus, scorpion, analog peptides, antimicrobial agents, nanotechnology, synergy.

PAGES: 101
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

The emergence of microorganisms resistant to conventional drugs consti-tutesaseriousglobalpublichealthissuethatlimitstherapeuticoptionsand underscores the urgent need for the discovery of new antimicrobialagents.ThevenomofthescorpionTityusstigmurusservesasarichsource of biologically active components, including antimicrobial peptideswith high therapeutic potential. Stigmurin, an antimicrobial peptide withantibiotic activity against Gram-positive bacterial strains, was used as aprototype for structural modifications, resulting in the generation of 31analogs (patent BR102015029044-6). In this study, the three-dimensionalconformation was elucidated using nuclear magnetic resonance (NMR),stability was investigated through circular dichroism, and the in vitro andin vivo antibacterial action of two analog peptides of Stigmurin, namedStigA25 and StigA31, was assessed. In addition to the remarkable antimi-crobial activity described in a previous study, StigA25 and StigA31 exhib-ited concentration-dependent hemolytic activity compared to the proto-type peptide. To mitigate cytotoxicity, enhance stability, and optimizetherapeutic efficiency of these peptides, the effect of associating thesebioactive components with poly(lactic-co-glycolic acid) (PLGA) nanopar-ticles was investigated. StigA25 and StigA31 displayed a predominant α-helical conformation by NMR, with high structural stability under varioustemperature, pH, and salt conditions as determined by circular dichroism.The incorporation of these components into PLGA nanoparticles resultedinastablenanosystemwithantimicrobialactivityequivalenttothatoffree peptides and a significant reduction in toxicity. Scanning and trans-mission electron microscopy demonstrated that both free and nanoparticulated peptides exerted their action on the bacterial cell membrane, causingmembrane disruption. Therefore, this study reveals the high therapeuticpotential of StigA25 and StigA31 when associated with PLGA nanosystems, suggesting the use of this nanocarrier as a promising tool for thetherapeutic application of these bioactive molecules in the development ofnewanti-infectious agents.

COMMITTEE MEMBERS:
Externo ao Programa - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR - nullExterno à Instituição - ENEAS DE CARVALHO - IB/SP
Interno - 2275890 - MARCELO DE SOUSA DA SILVA
Externa à Instituição - MARIANA DE SOUZA CASTRO - UnB
Presidente - 1544647 - MATHEUS DE FREITAS FERNANDES PEDROSA