Guo Qiao, Wu Qiaolian, Bai Dangdang, Liu Yang, Chen Lin, Jin Sheng, Wu Yuting, Duan Kangmin
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, Shaanxi, China.
Department of Burns and Cutaneous Surgery, the Fourth Military Medical University, Xi'an, Shaanxi, China.
Antimicrob Agents Chemother. 2016 Nov 21;60(12):7159-7169. doi: 10.1128/AAC.01357-16. Print 2016 Dec.
Dimethyl sulfoxide (DMSO) is commonly used as a solvent to dissolve water-insoluble drugs or other test samples in both in vivo and in vitro experiments. It was observed during our experiment that DMSO at noninhibitory concentrations could significantly inhibit pyocyanin production in the human pathogen Pseudomonas aeruginosa Pyocyanin is an important pathogenic factor whose production is controlled by a cell density-dependent quorum-sensing (QS) system. Investigation of the effect of DMSO on QS showed that DMSO has significant QS antagonistic activities and concentrations of DMSO in the micromolar range attenuated a battery of QS-controlled virulence factors, including rhamnolipid, elastase, and LasA protease production and biofilm formation. Further study indicated that DMSO inhibition of biofilm formation and pyocyanin production was attained by reducing the level of production of an autoinducer molecule of the rhl QS system, N-butanoyl-l-homoserine lactone (C-HSL). In a mouse model of a burn wound infection with P. aeruginosa, treatment with DMSO significantly decreased mouse mortality compared with that for mice in the control group. The capacity of DMSO to attenuate the pathogenicity of P. aeruginosa points to the potential use of DMSO as an antipathogenic agent for the treatment of P. aeruginosa infection. As a commonly used solvent, however, DMSO's impact on bacterial virulence calls for cautionary attention in its usage in biological, medicinal, and clinical studies.
二甲基亚砜（DMSO）在体内和体外实验中通常用作溶剂，以溶解水不溶性药物或其他测试样品。在我们的实验中观察到，在非抑制浓度下，DMSO可显著抑制人类病原体铜绿假单胞菌中绿脓菌素的产生。绿脓菌素是一种重要的致病因子，其产生受细胞密度依赖性群体感应（QS）系统控制。对DMSO对QS影响的研究表明，DMSO具有显著的QS拮抗活性，微摩尔范围内的DMSO浓度可减弱一系列QS控制的毒力因子，包括鼠李糖脂、弹性蛋白酶和LasA蛋白酶的产生以及生物膜形成。进一步研究表明，DMSO对生物膜形成和绿脓菌素产生的抑制作用是通过降低rhl QS系统的自诱导分子N-丁酰基-L-高丝氨酸内酯（C4-HSL）的产生水平来实现的。在铜绿假单胞菌烧伤伤口感染的小鼠模型中，与对照组小鼠相比，用DMSO治疗可显著降低小鼠死亡率。DMSO减弱铜绿假单胞菌致病性的能力表明，DMSO有可能作为一种抗病原体剂用于治疗铜绿假单胞菌感染。然而，作为一种常用溶剂，DMSO对细菌毒力的影响在生物学、医学和临床研究中的使用需要谨慎关注。
