Exploring the potential of azole compounds as efflux pump inhibitors and biofilm formation inhibitors for multidrug-resistant Staphylococcus aureus
學生姓名:
江立荷
指導教授:
林泓廷
學期:
113上
摘 要:
The widespread use and misuse of antibiotics have led to the emergence of antibiotic resistance globally, with some strains exhibiting multidrug resistance. Staphylococcus aureus, a common human pathogen, employs multiple resistance mechanisms, with efflux pumps playing a key role by constituting 6–18% of bacterial transport proteins and promoting biofilm formation and adhesion. Certain efflux pump inhibitors (EPIs) have shown promise in reducing biofilm formation. This study explores azole compounds targeting the Staphylococcus aureus efflux pumps NorA and Tet (K). The results indicate that two bioactive isomers of ketoconazole, 2S, 4R and 2R, 4S, exhibit high affinity with the Major Facilitator Superfamily (MFS) representative structure 1PW4, while five other azole compounds in another study show extremely
high affinity with Tet (K). These azole compounds reduced the minimum inhibitory concentration (MIC) of antibiotics by 32–1024 -fold in synergy assays and significantly increased EtBr accumulation, with both studies demonstrating maximum bactericidal activity in time-kill assays at 8–24 hours, respectively, and effectively reducing biofilm formation. As FDA-approved EPI candidates, these compounds may have practical applications in clinical therapy. A combination of tetracycline and azole drugs could serve as a potential anti-infective treatment, especially for persistent Staphylococcus aureus surface infections associated with robust biofilm formation.
high affinity with Tet (K). These azole compounds reduced the minimum inhibitory concentration (MIC) of antibiotics by 32–1024 -fold in synergy assays and significantly increased EtBr accumulation, with both studies demonstrating maximum bactericidal activity in time-kill assays at 8–24 hours, respectively, and effectively reducing biofilm formation. As FDA-approved EPI candidates, these compounds may have practical applications in clinical therapy. A combination of tetracycline and azole drugs could serve as a potential anti-infective treatment, especially for persistent Staphylococcus aureus surface infections associated with robust biofilm formation.