Banca de DEFESA: KESIA XISTO DA FONSECA RIBEIRO DE SENA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : KESIA XISTO DA FONSECA RIBEIRO DE SENA
DATE: 13/06/2022
TIME: 09:00
LOCAL: Auditório do Departamento de Antibióticos
TITLE:

ANTIMICROBIAL ACTIVITY OF THIAZOLIDINE-2,4-DIONE AND 4-THIOXOTHIAZOLIDINE-2-ONE DERIVATIVES AGAINST MULTIDRUG-RESISTANT Staphylococcus aureus CLINICAL ISOLATES

KEY WORDS:

Biofilm, cytotoxicity, Caenorhabditis elegans, SEM

PAGES: 139
BIG AREA: Ciências Biológicas
AREA: Microbiologia
SUMMARY:

Healthcare-associated infections (HAI) are frequent and represent a serious global health problem. Staphylococcus aureus is the most common human pathogen and one of the main causative agents of HAI. Thiazolidines are a pharmacophoric group of interest in the development of new drugs due to their many biological activities, such as antimicrobial. The aim of this study was to evaluate the antimicrobial and antibiofilm activities of two analog series of thiazolidine-2,4-dione and 4-thioxothiazolidine-2-one against multidrug-resistant Staphylococcus aureus clinical isolates. Twenty S. aureus clinical isolates were evaluated for the presence of antimicrobial resistance genes (vanA, mecA, norA, and ermA) and biofilm formation. We determined the MIC and MBC, time- to-kill, antibiofilm, in vivo antimicrobial activity, and morphological changes induced by the thiazolidine derivatives, as well as their cytotoxicity. The mecA, norA, and ermA genes were found in 95%, 95% and 80% of S. aureus clinical isolates, respectively. None of the isolates had the vanA gene. All clinical isolates were biofilm formers, 85% of them classified as strongly adherent. The most active derivatives (1a, 2a, and 2b) showed MIC between 1 and 16 μg/mL, with time-to-kill curves showing a bactericidal effect up to 24 h. In the antibiofilm assay, the most active derivatives were able to inhibit about 90% of biofilm formation. The 5-benzylidene-4-thioxothiazolidine-2-one derivatives were more active against planktonic S. aureus, while the 5-benzylidene-thiazolidine-2,4-dione derivatives were able to disrupt about 50% of the mature biofilm. In the in vivo infection model using Caenorhabditis elegans as a host, the derivatives 1a, 2a, and 2b increased nematode survival with a concentration-dependent effect. Exposure of S. aureus to the derivatives 2a and 2b induced surface changes and decrease cell size. None of the derivatives was cytotoxic for human peripheral blood mononuclear cells (PBMC) but showed moderate cytotoxicity for L929 fibroblasts. Only derivative 2b showed a selectivity index greater than 10 for both cells. Thus, these derivatives are drug candidates for the development of new antimicrobials.

BANKING MEMBERS:
Interna - 1736206 - GLAUCIA MANOELLA DE SOUZA LIMA
Externa à Instituição - JULIANNA FERREIRA CAVALCANTI DE ALBUQUERQUE
Externa ao Programa - 1223220 - MARIA AMELIA VIEIRA MACIEL
Externa ao Programa - 1134731 - NORMA BUARQUE DE GUSMAO
Presidente - 2726820 - RAFAEL MATOS XIMENES
Interna - 1217065 - TERESINHA GONCALVES DA SILVA