RESUMO
The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the ompA promoter activity of A. baumannii, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the ompA expression and biofilm formation in A. baumannii ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging A. baumannii strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with A. baumannii ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.
Assuntos
Infecções por Acinetobacter/prevenção & controle , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/genética , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/fisiologia , Animais , Antibacterianos/administração & dosagem , Proteínas da Membrana Bacteriana Externa/metabolismo , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Humanos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana/métodos , Regiões Promotoras Genéticas/genética , Bibliotecas de Moléculas Pequenas/administração & dosagem , Bibliotecas de Moléculas Pequenas/farmacologia , Análise de SobrevidaRESUMO
Volatile compounds of coffee brewed under various roasting conditions and by different brewing methods were analyzed. Green coffee beans (Coffea arabica) were roasted at 235 °C for 13 min, 240 °C for 15 min, and 245 °C for 17 min. Roasted coffee beans were ground into particles of three different sizes (710, 500, and 355 µm) and brewed by an espresso coffee machine and the cold brew method. Three types of water (filtered, tap, and bottled) were used for coffee extraction. SPME-GC-MS results indicated that increasing the roasting temperature and time increased the levels of 2,2'-methylene-bis-furan, guaiacol, and 4-ethylguaiacol (p < 0.05) and decreased the levels of furfural (p < 0.05). Grind size was inversely proportional to the measured signal of volatiles by GC-MS (p < 0.05). The measured GC/MS intensities of 2-methylpyrazine, 2,5-dimethylpyrazine, and 2-methoxy-4-vinylphenol were significantly higher in coffee brewed with filtered water (p < 0.05) than tap and bottled water. 2-Methylpyrazine, 1-methylpyrrole, and 2-acetylfuran were the most abundant components in the cold brew. Overall, roasting conditions and extraction methods were determined to be significant factors for volatile compounds in coffee. This is the first study showing the analysis of volatile compounds in coffee according to various types of water and extraction methods, such as espresso and cold brew coffee.
