抗生素耐药基因古老起源与现代进化及其警示

Ancient origin and modern evolution of antibiotic resistome and their implications

细菌抗生素耐药性系全球关注的医学及社会问题。新近对古老细菌DNA与现代病原菌的研究揭示了抗生素耐药基因的古老起源、多样性及快速的现代进化,并促使了耐药基因组(resistome)的问世。耐药基因决定簇及其与进化有关的基因可移动元件如质粒、插入顺序、转座子和整合子等远存在于人类抗生素时代之前。在过去短短的70年抗生素时代期间,人类大量应用各类抗生素等行为明显地造成了对细菌的选择性压力,加之细菌基因本身的自突变性和水平基因转移能力等多种因素促使了耐药基因的进化及新型耐药特征的出现。人类重要病原菌如ESKAPE病原菌(肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠道杆菌属)所呈现的高度多重耐药性或泛耐药性便充分展示了耐药基因起源、进化和传播的复杂性,并严重地威胁着感染性疾病的治疗。所有这些均警示人类需要同时采取多种有效措施控制各类抗生素尤其是人类极为重要抗生素的使用。任何环境下的抗生素滥用当止!

Antibiotic resistance in bacteria has emerged as both medical and social problems worldwide. Research advances on ancient bacterial DNA and modern pathogens have indicated the ancient origin, diversity and rapid evolution of antibiotic resistance genes or resistome. Resistance determinants and those mobile genetic elements related to gene evolution such as plasmids, insertion sequences, transposons and integrons have existed far before the modem antibiotic era. During the short period of the past 70 years of the antibiotic era, the significant use of antibiotics has created selection pressures on bacteria. Moreover, bacteria themselves possess spontaneous mutations as well as horizontal gene transfer. These factors have led to the rapid evolution of resistance genes and the emergence of new resistance features. There exists a shared antibiotic resistome between the environmental bacteria and human pathogens. The key human pathogens such as the ESKAPE pathogens with high levels of multidrug or pan-drug resistance have not only demonstrated the complexity of the origin, evolution and spread of resistance genes but also constituted a significant threat against anti-infective therapy. All of these have revealed an urgent need to further take effective measures to control the use of various antibiotics, particularly those belonging to the critically-important antibiotics in human medicine. Antibiotic abuse must be stopped in all environments!