Antibacterial Characterization of Novel Synthetic Thiazole Compounds against Methicillin-Resistant Staphylococcus pseudintermedius

摘要: Staphylococcus pseudintermedius is a commensal organism of companion animals that significant source opportunistic infections in dogs. With the emergence clinical isolates S. (chiefly methicillin-resistant (MRSP)) exhibiting increased resistance to nearly all antibiotic classes, new antimicrobials and therapeutic strategies are urgently needed. Thiazole compounds have been previously shown possess potent antibacterial activity against multidrug-resistant strains aureus human animal concern. Given genetic similarity between pseudintermedius, this study explores potential use thiazole as novel agents methicillin-sensitive (MSSP) MRSP. A broth microdilution assay confirmed these exhibit bactericidal (at sub-microgram/mL concentrations) both MSSA MRSP while MTS three 10 μg/mL) were not toxic mammalian cells. time-kill revealed two derivatives rapidly kill within hours. However, rapid was due disruption bacterial cell membrane indicating an alternative mechanism action for multi-step selection analysis 4 5 exhibited modest (two-fold) shift over ten passages. Furthermore, six subinihibitory concentration) demonstrated ability re-sensitize oxacillin, extending utility β-lactam antibiotics Metabolic stability with dog liver microsomes compound 3 improved physicochemical profile compared lead compound. In addition this, possessed long post-antibiotic effect least 8 hours) Collectively present demonstrates synthetic MSSP warrant further investigation into their antimicrobial agents.