β-lactamase inhibitory potential of kalafungin from marine Streptomyces in Staphylococcus aureus infected zebrafish

β-lactamase inhibitors are potent synergistic drugs to deteriorate the multidrug-resistant bacteria. Here, we report the β-lactamase inhibitory ability of kalafungin isolated from a marine Sponge derived Streptomyces sp. SBRK1. The IC₅₀ value of the kalafungin was calculated as 225.37 ± 1.95 μM against β-lactamase. The Enzyme kinetic analysis showed the Km value of 3.448 ± 0.7 μM and V_max value of 215.356 ± 8 μM/min and the inhibition mechanism was identified as uncompetitive type. Along with the Antibacterial activity, the cell surface analysis of kalafungin treated Staphylococcus aureus cells revealed destruction of cell membrane in response to β-lactamase inhibition. Molecular docking studies have confirmed the binding property of kalafungin against β-lactamase with two hydrogen bonds. In vivo efficacy studies in the zebrafish model by green fluorescent protein expressing S. aureus Infection, survival, safety and behavioral profile were reported. The toxicity and Anti-infection revealed that the compound was evidently active and safe to all organs. In conclusion, this is the first report on kalafungin with β- lactamase inhibition and suggests that kalafungin may useful for synergic Antibacterial therapy with β-lactam drugs to overcome β-lactamase-based resistance of any Bacterial pathogens.

Kalafungin; Molecular docking; Streptomyces; Zebrafish embryo; β-lactamase inhibitor.