RESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the main human pathogens and is responsible for many diseases, ranging from skin infections to more invasive infections. These infections are dangerous and expensive to treat because these strains are resistant to a large number of conventional antibiotics. Thus, the antibacterial effect of ketamine against MRSA strains, its mechanism of action, and in silico interaction with sortase A were evaluated. The antibacterial effect of ketamine was assessed using the broth microdilution method. Subsequently, the mechanism of action was assessed using flow cytometry and molecular docking assays with sortase A. Our results showed that ketamine has a significant antibacterial activity against MRSA strains in the range of 2.49-3.73 mM. Their mechanism of action involves alterations in membrane integrity and DNA damage, reducing cell viability, and inducing apoptosis. In addition, ketamine had an affinity for S. aureus sortase A. These results indicate that this compound can be used as an alternative to develop new strategies to combat infections caused by MRSA.
Assuntos
Ketamina , Staphylococcus aureus Resistente à Meticilina , Aminoaciltransferases , Antibacterianos/farmacologia , Proteínas de Bactérias , Cisteína Endopeptidases , Humanos , Ketamina/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Staphylococcus aureusRESUMO
Antibiotic misuse and overuse in both the healthcare and agricultural fields have dramatically increased the prevalence of antibiotic resistance in human pathogens. Two strains of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43330 and a wild-type) and 1 strain of methicillin-susceptible S. aureus (ATCC 25923) were challenged (9 runs in triplicate) in a preliminary study with ultraviolet germicidal irradiation (UVGI) doses ranging from 0.25 to 3.00 mJ/cm(2). The mean percent kill was calculated for each strain when compared with the control plates (no exposure to UVGI). Then, each strain was challenged (22 runs in triplicate) with UVGI doses of 2.00, 2.50, and 3.00 mJ/cm(2). The results suggest a difference between the doses required to disinfect surfaces with each strain. Assuming a standard error rate of α = 0.05, there was a significant difference in variance between the MRSA (ATCC 43330 and wild type) strains and the S. aureus (ATCC 25923) methicillin-susceptible strain.