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.

β-内酰胺酶抑制剂是使多重耐药菌变质的强效协同药物。在这里，我们报告了从海绵来源的链霉菌属中分离的卡拉芬净的 β-内酰胺酶抑制能力。SBRK1。卡拉芬净对 β-内酰胺酶的 IC ₅₀值计算为 225.37 ± 1.95 μM。酶动力学分析表明3.448±0.7μM的Km值和V_最大的215.356±8μM/分钟值和抑制机制被确定为无竞争类型。随着抗菌活性，卡拉芬净处理金黄色葡萄球菌的细胞表面分析细胞显示出响应β-内酰胺酶抑制的细胞膜破坏。分子对接研究证实了卡拉芬净对具有两个氢键的 β-内酰胺酶的结合特性。报道了通过表达金黄色葡萄球菌感染、存活、安全性和行为特征的绿色荧光蛋白在斑马鱼模型中进行的体内功效研究。毒性和抗感染性表明该化合物对所有器官均具有明显的活性和安全性。总之，这是关于具有 β-内酰胺酶抑制作用的 kalafungin 的第一份报告，并表明 kalafungin 可用于与 β-内酰胺药物协同抗菌治疗，以克服任何细菌病原体的基于 β-内酰胺酶的耐药性。