有机污染物对抗生素抗性基因水平转移的影响及机制

Organic contaminants influence the horizontal transfer of antibiotic resistance genes

基因水平转移是抗生素抗性基因(antibiotic resistance genes, ARGs)在环境中广泛传播的主要途径.环境中常见的有机污染物可通过对ARGs水平转移产生影响而改变其丰度与分布.近年来,有机污染物如何影响ARGs水平转移过程已成为备受关注的研究热点,相关研究取得一些进展. ARGs水平转移方式主要有接合、转化及转导.接合是原核生物界中存在最广泛、贡献最大的基因水平转移方式.除褪黑激素外,多数有机污染物可通过施加选择性压力、引起氧化应激反应、改变细胞膜通透性和细胞接触效率、调节三磷酸腺苷(ATP)合成和群体感应等机制促进ARGs接合转移,且促进作用受污染物浓度调控.关于转化转移的研究相对有限,多集中于探讨新型污染物的影响效应.与接合转移相似,多数有机污染物促进了ARGs转化,但多环芳烃表现出抑制作用.有机污染物对ARGs转化产生影响的有效浓度多在μg/L和mg/L量级,作用时间也是调控其影响效用的关键因素.其影响ARGs转化的机制主要包括:影响ARGs载体的结构与功能、协助DNA抵御胞外酶降解、促进胞内活性氧自由基(reactive oxygen species, ROS)生成、增强细胞膜通透性或增加细胞膜通道、提高细胞感受能力、促进用于搜索胞外DNA的菌毛形成、提高ARGs整合进基因组的几率.虽然理论上有机污染物对ARGs转导存在影响潜力,但相关研究仍几近空白.今后研究需关注有机污染物对ARGs转化、转导以及由膜囊泡介导的一种新型水平转移方式的影响,并尝试使用土著微生物和多类型质粒作为研究对象、在类环境条件下开展研究.

Horizontal gene transfer is a vital way for antibiotic resistance genes(ARGs) to disseminate in the environment, through which pathogens may possess high opportunities to acquire antibiotic resistance, thus threatening human health and ecological safety. Organic contaminants are widespread in environmental media and frequently co-exist with ARGs.Organic contaminants strongly affect the abundance and distribution of ARGs in ecological niches, and their influence on horizontal gene transfer is regarded as a crucial mechanism. Based on this, the influence of organic contaminants on the horizontal transfer of ARGs has drawn more and more concerns in recent years, and some meaningful progress has been made in this field. Therefore, this review will summarize the relevant advancement and point out the future direction of the studies.Horizontal gene transfer occurs majorly in three ways: conjugation, transformation and transduction. Conjugation means the donor cells and recipient cells physically contact each other, and the genetic material will be transferred through the contacting sites. Most organic contaminants can promote conjugative transfer, and merely the melatonin inhibits this process. They affect the conjugative transfer of ARGs mainly through the following mechanisms: posing selective pressures, inducing oxidative stress response, altering the cell membrane permeability, increasing the intercellular contacting efficiency, and regulating the adenosine triphosphate(ATP) synthesis and intercellular quorum sensing.Transformation refers to the competent cells acquiring extracellular genetic material from surrounding environments and integrating them into their genomes. The studies concerning transformation are relatively limited, focusing on the influence of some emerging contaminants. Like conjugation, most of the tested organic contaminants exert an enhancing effect on the ARG transformation, and only polycyclic aromatic hydrocarbons suppress this process. Organic contaminants would influence ARG transformation from two aspects: reacting on the extracellular DNA(e.g., plasmids) and reacting on the recipient cells. By reacting on extracellular DNA, they may interact with the DNA and thus induce aggregation of antibiotic resistance plasmids, impact the transcription of ARGs, and assist the plasmid against the degradation of extracellular enzymes, thereby affecting the transformation process. By reacting on recipient cells, they facilitate the generation of intracellular reactive oxide species, promote cell membrane permeability, increase the number of membrane channels,enhance the cell competence, promote the formation of DNA-searching pilus, and increase the probability of ARGs integrating into the host genomes. Transduction is a process in which the genetic material is transferred by the phages. The influence of organic contaminants on transduction has been rarely studied. However, according to the influencing mechanism of nanoparticles on transduction, organic contaminants may also have the potential to affect this process.Due to limited studies on transformation and transduction, future studies should pay more attention to these two research fields. Besides, since previous research was usually carried out by applying very few types of microorganisms and plasmids under laboratory conditions, more studies should be done by utilizing some indigenous environmental microorganisms and more types of plasmids and simulating environmental conditions. Furthermore, apart from conjugation, transformation,and transduction, a new mode of horizontal gene transfer has been recently reported that is mediated by the membrane vesicles, which has drawn considerable attention. Whether organic contaminants could affect the membrane vesiclemediated gene transfer is a fascinating question awaiting future exploration.