Antibacterial Activity and Mechanism of Canagliflozin against Methicillin-Resistant Staphylococcus aureus

Diabetic foot infection (DFI) is a common complication in diabetes patients, with infections being the leading cause of amputations. Staphylococcus aureus frequently found diabetic infections, which methicillin-resistant (MRSA) has become major clinical and epidemiological challenge. Since MRSA strains are resistant to most β-lactam antibiotics, also partially other treatment difficult costly. The emergence drug-resistant bacteria often arises from overuse or misuse antibiotics. Clinically, canagliflozin commonly used for type 2 diabetes. On this basis, we investigated antibacterial activity mechanism against MRSA, aim discover novel functions provide new insights MRSA. Using microbroth dilution method determine half maximal inhibitory concentration drugs, that not only can inhibit growth methicillin-sensitive (MSSA) but exhibits IC50 values, at approximately 56.01 μM 57.60 μM, were almost same. At 12 h, showed significant effect above 30 μM. In addition, its combined use penicillin achieved better effects, increased by about three times. Additive (FICI = 0.69) was between canagliflozin, than doxycycline 0.95). Canagliflozin affected bacterial metabolic markers, such as glucose, ATP, lactic acid. results crystal violet staining indicate disrupted formation biofilm. Our electron microscopy distorted cell wall. RT-PCR suggest down-regulated expressions biofilm-related gene (clfA, cna, agrC, mgrA, hld) methicillin-resistance (mecA), related Molecular docking indicated some interesting targets sarA, crtM fnbA proteins. conclusion, affecting metabolism, inhibiting biofilm formation, distorting wall, altering expression virulence. study reveals providing reference treating infections.