Woo Seung-Gyun, Lee So-Min, Lee So-Yeon, Lim Kyoung-Hee, Ha Eun-Ju, Kim Sa-Hyun, Eom Yong-Bin
Department of Medical Sciences, College of Medical Sciences, Soonchunhyang University, Asan, 31538, Republic of Korea.
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, 22 Soonchunhyang-ro, Asan, Chungcheongnam-do, 31538, Republic of Korea.
Arch Microbiol. 2017 Oct;199(8):1151-1163. doi: 10.1007/s00203-017-1386-x. Epub 2017 May 9.
Human pathogens have readily been converted into multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), because of the long-term use of conventional antibiotics. In addition, the biofilms formed by S. aureus cells are especially problematic and are related to the persistence of chronic infections because they constitute a major mechanism of promoting tolerance to diverse antimicrobial agents. Hence, the inhibitions of biofilm formation and/or toxin production are accepted as alternative means of controlling S. aureus infections. The present study was aimed at identifying novel anti-biofilm and/or anti-virulence compounds in friedelane-based pentacyclic triterpenoids present in many edible and medicinal plants-and investigating them against MRSA strains. As a result, dihydrocelastrol and dihydrocelastryl diacetate were found to both inhibit the biofilm formation of, and to disrupt the preformed biofilms of, MRSA strains to an increasingly greater degree with increasing concentrations of each compound. Furthermore, these two triterpenoids also clearly inhibited the hemolytic activity of MRSA-and in-line with their anti-biofilm activities, rendered the cell more hydrophilic. Additionally, corroborating phenotypic results, transcriptional analyses showed that both dihydrocelastrol and dihydrocelastryl diacetate disturbed the expression of gene related to α-hemolysin (hla) and down-regulated the expressions of the crucial biofilm-associated genes (agrA, sarA, ica, RNAIII, and rbf) in MRSA. The findings of this study suggest that friedelane-based pentacyclic triterpenoids-especially dihydrocelastrol and dihydrocelastryl diacetate-have the potential to be candidates both for use in controlling biofilm-related infections and for use as important components of anti-virulence strategies for fighting against MRSA infection.
由于长期使用传统抗生素，人类病原体很容易转变为多重耐药病原体，如耐甲氧西林金黄色葡萄球菌（MRSA）。此外，金黄色葡萄球菌细胞形成的生物膜尤其成问题，并且与慢性感染的持续存在有关，因为它们构成了促进对多种抗菌剂耐受性的主要机制。因此，抑制生物膜形成和/或毒素产生被认为是控制金黄色葡萄球菌感染的替代手段。本研究旨在从许多食用和药用植物中存在的基于木栓烷的五环三萜类化合物中鉴定新型抗生物膜和/或抗毒力化合物，并针对MRSA菌株对其进行研究。结果发现，随着每种化合物浓度的增加，二氢雷公藤红素和二氢雷公藤红素二乙酸酯对MRSA菌株生物膜形成的抑制作用以及对已形成生物膜的破坏作用越来越大。此外，这两种三萜类化合物还明显抑制了MRSA的溶血活性，并且与它们的抗生物膜活性一致，使细胞更具亲水性。此外，与表型结果一致，转录分析表明，二氢雷公藤红素和二氢雷公藤红素二乙酸酯均扰乱了与α-溶血素（hla）相关基因的表达，并下调了MRSA中关键生物膜相关基因（agrA、sarA、ica、RNAIII和rbf）的表达。本研究结果表明，基于木栓烷的五环三萜类化合物，尤其是二氢雷公藤红素和二氢雷公藤红素二乙酸酯，有潜力成为控制生物膜相关感染的候选药物，以及作为对抗MRSA感染的抗毒力策略的重要组成部分。
