Salaheen Serajus, Peng Mengfei, Joo Jungsoo, Teramoto Hironori, Biswas Debabrata
Department of Animal and Avian Sciences, University of Maryland College Park, MD, USA.
Department of Animal and Avian Sciences, University of MarylandCollege Park, MD, USA; Biological Sciences Program - Molecular and Cellular Biology, University of MarylandCollege Park, MD, USA.
Front Microbiol. 2017 Feb 21;8:253. doi: 10.3389/fmicb.2017.00253. eCollection 2017.
The therapeutic roles of phenolic blueberry () and blackberry () pomace (commercial byproduct) extracts (BPE) and their mechanism of actions were evaluated against methicillin resistant (MRSA). Five major phenolic acids of BPE, e.g., protocatechuic, p. coumaric, vanillic, caffeic, and gallic acids, as well as crude BPE completely inhibited the growth of vegetative MRSA while BPE+methicillin significantly reduced MRSA biofilm formation on plastic surface. In addition, BPE restored the effectiveness of methicillin against MRSA by down-regulating the expression of methicillin resistance () and efflux pump (, , , , , and ) genes. Antibiogram with broth microdilution method showed that MIC of methicillin reduced from 512 μg/mL to 4 μg/mL when combined with only 200 μg Gallic Acid Equivalent (GAE)/mL of BPE. Significant reduction in MRSA adherence to and invasion into human skin keratinocyte Hek001 cells were also noticed in the presence of BPE. BPE induced anti-apoptosis and anti-autophagy pathways through overexpression of gene and down-regulation of and genes (inducers of apoptosis pathway) in Hek001 cells. In summary, novel and sustainable prophylactic therapy can be developed with BPE in combination with currently available antibiotics, especially methicillin, against skin and soft tissue infections with MRSA.
评估了酚类蓝莓和黑莓果渣（商业副产品）提取物（BPE）对耐甲氧西林金黄色葡萄球菌（MRSA）的治疗作用及其作用机制。BPE的五种主要酚酸，即原儿茶酸、对香豆酸、香草酸、咖啡酸和没食子酸，以及粗制BPE完全抑制了MRSA营养细胞的生长，而BPE+甲氧西林显著减少了塑料表面MRSA生物膜的形成。此外，BPE通过下调甲氧西林抗性（）和外排泵（、、、、和）基因的表达，恢复了甲氧西林对MRSA的有效性。采用肉汤微量稀释法进行的药敏试验表明，当仅与200μg没食子酸当量（GAE）/mL的BPE联合使用时，甲氧西林的最低抑菌浓度（MIC）从512μg/mL降至4μg/mL。在存在BPE的情况下，还注意到MRSA对人皮肤角质形成细胞Hek001细胞的粘附和侵袭显著减少。BPE通过Hek001细胞中基因的过表达和凋亡途径诱导基因（凋亡途径诱导剂）和基因的下调，诱导抗凋亡和抗自噬途径。总之，可开发出BPE与目前可用抗生素（尤其是甲氧西林）联合使用的新型可持续预防性疗法，用于治疗MRSA引起的皮肤和软组织感染。
