Microbial Ecology Research Laboratory, Department of Biotechnology, The Neotia University, Sarisha, West Bengal, 743368, India.
Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F Nilgunj Road, Panihati, Kolkata, West Bengal, 700114, India.
Microb Pathog. 2024 Apr;189:106601. doi: 10.1016/j.micpath.2024.106601. Epub 2024 Feb 27.
Methicillin-resistant Staphylococcus aureus (MRSA), a drug-resistant human pathogen causes several nosocomial as well as community-acquired infections involving biofilm machinery. Hence, it has gained a wide interest within the scientific community to impede biofilm-induced MRSA-associated health complications. The current study focuses on the utilization of a natural bioactive compound called piperine to control the biofilm development of MRSA. Quantitative assessments like crystal violet, total protein recovery, and fluorescein-di-acetate (FDA) hydrolysis assays, demonstrated that piperine (8 and 16 μg/mL) could effectively compromise the biofilm formation of MRSA. Light and scanning electron microscopic image analysis confirmed the same. Further investigation revealed that piperine could reduce extracellular polysaccharide production by down-regulating the expression of icaA gene. Besides, piperine could reduce the cell-surface hydrophobicity of MRSA, a crucial factor of biofilm formation. Moreover, the introduction of piperine could interfere with microbial motility indicating the interaction of piperine with the quorum-sensing components. A molecular dynamics study showed a stable binding between piperine and AgrA protein (regulator of quorum sensing) suggesting the possible meddling of piperine in quorum-sensing of MRSA. Additionally, the exposure to piperine led to the accumulation of intracellular reactive oxygen species (ROS) and potentially heightened cell membrane permeability in inhibiting microbial biofilm formation. Besides, piperine could reduce the secretion of diverse virulence factors from MRSA. Further exploration revealed that piperine interacted with extracellular DNA (e-DNA), causing disintegration by weakening the biofilm architecture. Conclusively, this study suggests that piperine could be a potential antibiofilm molecule against MRSA-associated biofilm infections.
耐甲氧西林金黄色葡萄球菌（MRSA）是一种耐药的人类病原体，可引起多种医院获得性和社区获得性感染，涉及生物膜机制。因此，科学界广泛关注抑制生物膜诱导的 MRSA 相关健康并发症。本研究侧重于利用一种称为胡椒碱的天然生物活性化合物来控制 MRSA 的生物膜发育。结晶紫、总蛋白回收和荧光素二乙酸（FDA）水解测定等定量评估表明，胡椒碱（8 和 16μg/mL）可有效破坏 MRSA 的生物膜形成。光和扫描电子显微镜图像分析证实了这一点。进一步的研究表明，胡椒碱可以通过下调 icaA 基因的表达来减少细胞外多糖的产生。此外，胡椒碱可以降低 MRSA 的细胞表面疏水性，这是生物膜形成的关键因素。此外，胡椒碱的引入可以干扰微生物的运动性，表明胡椒碱与群体感应成分的相互作用。分子动力学研究表明胡椒碱与 AgrA 蛋白（群体感应调节剂）之间存在稳定的结合，表明胡椒碱可能干扰 MRSA 的群体感应。此外，暴露于胡椒碱会导致细胞内活性氧（ROS）的积累，并可能通过提高细胞膜通透性来抑制微生物生物膜的形成。此外，胡椒碱可以减少 MRSA 多种毒力因子的分泌。进一步的探索表明，胡椒碱与细胞外 DNA（e-DNA）相互作用，通过削弱生物膜结构导致其解体。总之，这项研究表明，胡椒碱可能是一种针对 MRSA 相关生物膜感染的潜在抗生物膜分子。
