Negi Abhishek, Kuo Chia-Wei, Hazam Prakash Kishore, Yeh Jih-Chao, Lin Wen-Chun, Lou Yuan-Chao, Yu Chao-Yuan, Yu Tsai-Luen, Lu Tsai-Ming, Chen Jyh-Yih
Molecular and Biological Agricultural Science Program, International Graduate Program, Academia Sinica, Taipei, 11529, Taiwan.
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, 402, Taiwan.
Probiotics Antimicrob Proteins. 2025 Apr 14. doi: 10.1007/s12602-025-10535-0.
Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat to public health due to its resistance to conventional antibiotics and its ability to form robust biofilms on both biotic and abiotic surfaces. In this study, we explore the novel mechanisms by which deep-sea-derived probiotics serve as an alternative strategy to combat MRSA infections. Three promising probiotic candidates, Lactococcus lactis (L25_4) and two strains of Leuconostoc pseudomesenteroides (L25_6 and L25_7), were isolated from ocean water collected at a depth of 312 m off the eastern coast of Taiwan. Each candidate strain demonstrated potent antimicrobial activity, significantly reducing MRSA biofilm formation when applied to pork skin. The strains also improved survival rates in a Galleria mellonella infection model (> 90% survival). Immunomodulatory effects were evident, with marked upregulation of Cecropin antimicrobial peptide (AMP) and downregulation of Gloverin AMP in the host. Scanning and transmission electron microscopy (SEM and TEM) revealed that probiotic treatments compromised MRSA cell membrane integrity, consistent with transcriptomic analysis showing downregulation of genes related to protein translation, membrane structure, and transporter systems. Collectively, our comprehensive in vitro, in vivo, ex vivo, and transcriptomic analyses reveal the intricate mechanisms by which deep-sea probiotics modulate both host and MRSA gene expression, underscoring their potential as innovative tools for addressing antibiotic-resistant infections.
耐甲氧西林金黄色葡萄球菌（MRSA）因其对传统抗生素具有抗性以及能够在生物和非生物表面形成坚固的生物膜，对公众健康构成了重大威胁。在本研究中，我们探索了深海来源的益生菌作为对抗MRSA感染的替代策略的新机制。从台湾东海岸312米深处采集的海水中分离出三种有前景的益生菌候选菌株，乳酸乳球菌（L25_4）和两株假肠膜明串珠菌（L25_6和L25_7）。每种候选菌株都表现出强大的抗菌活性，应用于猪皮时能显著减少MRSA生物膜的形成。这些菌株在大蜡螟感染模型中也提高了存活率（存活率>90%）。免疫调节作用明显，宿主中抗菌肽天蚕素（AMP）显著上调，而格洛弗菌素AMP下调。扫描和透射电子显微镜（SEM和TEM）显示，益生菌处理破坏了MRSA细胞膜的完整性，这与转录组分析结果一致，即与蛋白质翻译、膜结构和转运系统相关的基因下调。总体而言，我们全面的体外、体内、离体和转录组分析揭示了深海益生菌调节宿主和MRSA基因表达的复杂机制，突出了它们作为解决抗生素耐药性感染的创新工具的潜力。
