Banca de QUALIFICAÇÃO: KESIA XISTO DA FONSECA RIBEIRO DE SENA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : KESIA XISTO DA FONSECA RIBEIRO DE SENA
DATE: 11/05/2022
LOCAL: Sala 03 - 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

PAGES: 136
BIG AREA: Ciências Biológicas
AREA: Microbiologia
SUMMARY:

Thiazolidines are heterocyclic compounds with a 5-membered saturated ring containing a thioether group and an amine group. These molecules have been drawing attention for having activity in several biological targets, mainly antimicrobial. 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. The aim of this study was to evaluate the antimicrobial and antibiofilm activities of thiazolidine-2,4-dione and 4-thioxothiazolidine-2-one derivatives against multidrug-resistant Staphylococcus aureus clinical isolates, comparing the effects of these analog series. 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, and in vivo antimicrobial activities of 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 C. elegans as host, the derivatives 1a, 2a, and 2b increased nematode survival with a concentration-dependent effect. None of the tested derivatives was cytotoxic (IC₅₀ > 100 μg/mL) 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 a promising framework for the development of new antimicrobial drugs.

BANKING MEMBERS:
Interna - 1736206 - GLAUCIA MANOELLA DE SOUZA LIMA
Externa ao Programa - 1134731 - NORMA BUARQUE DE GUSMAO
Presidente - 1217065 - TERESINHA GONCALVES DA SILVA