抗生素耐药基因质粒的适应性代价研究  

Fitness costs of plasmids carrying antibiotic resistance genes

作　　者：徐燕星 程浩[1] 胡小婕[1] 秦超 高彦征[1] XU YanXing;CHENG Hao;HU XiaoJie;QIN Chao;GAO YanZheng(Institute of Organic Contaminant Control and Soil Remediation,Nanjing Agricultural University,Nanjing 210095,China)

机构地区：[1]南京农业大学土壤有机污染控制与修复研究所,南京210095

出　　处：《中国科学:技术科学》2025年第4期662-680,共19页Scientia Sinica(Technologica)

基　　金：国家重点研发计划(批准号:2023YFC3708100,2023YFE0110800);国家自然科学基金(批准号:42430703,U22A20590)资助项目。

摘　　要：抗生素耐药性与细菌适应性密切相关,抗生素耐药基因(antibiotic resistance genes,ARGs)质粒在全球抗生素耐药性传播中发挥着重要作用.然而,ARGs质粒在促进宿主细菌适应多种环境的同时,也使宿主细菌产生了适应性代价.在抗生素选择压力下,ARGs质粒协助宿主细菌倾向于保留质粒以适应抗生素环境.在无抗生素选择压力下,携带ARGs质粒则使宿主细菌在整个生命周期中产生适应性代价,表现出生长-生存效应(生长速率和存活能力降低)、垂直-水平转移效应(转移方式改变和抑制质粒转移)以及细菌毒力效应(对宿主侵袭力降低和毒素分泌减少)等适应性代价效应,从而降低了与原始细菌的竞争力和生态位,甚至会从群体中消失.但宿主细菌仍可以通过一些途径(突变补偿性进化、非突变补偿进化以及接合转移)降低适应性代价,从而使其可以稳定持留在群体中.各种ARGs质粒适应性代价降低途径的发生,使仅通过控制抗生素滥用逆转细菌耐药性的驱动力变慢甚至停滞.今后应探究更多适应性代价降低途径的阻断方式以及不产生适应性代价的ARGs质粒的抗生素敏感性恢复方法,以多角度探索耐药性传播的限制途径,并尝试更多实际环境条件,以期为解决抗生素耐药危机提供新思路的同时,建立多角度的风险评估体系.Antibiotic resistance is linked to bacterial adaptability.Aside from that,antibiotic resistance genes(ARGs)carried by plasmids contribute tremendously to the global spread of antibiotic resistance.Nevertheless,while ARG plasmids facilitate the adaptation of host bacteria to various environments,they also impose a fitness cost on host bacteria.Under antibiotic selection pressure,ARG plasmids are advantageous to host bacteria as they increase their survival rate in the presence of antibiotics.In contrast,in the absence of antibiotic selection pressure,ARG plasmids cause fitness costs to the bacterial host.The fitness costs include growth-survival effects(lowered growth rate and viability),vertical-horizontal transfer effects(changes in the transfer mode and inhibition of ARGs plasmid transfer),and bacterial virulence effects(low host invasiveness and toxin secretion).Under such circumstances,this can not only lower the competitiveness and narrow the ecological niches of the host bacteria but can also eliminate them from the bacterial populations.Host bacteria can lessen fitness costs through several mechanisms(mutation-compensating evolution,nonmutational compensation,and conjugation transfer),which can help retain them in the population.Notably,the various reduction mechanisms of ARG plasmid fitness cost have impeded or even halted the reversal of bacterial resistance by controlling antibiotic misuse.Therefore,it is imperative to conduct research into mechanisms by which fitness cost reduction pathways can be blocked,and antibiotic susceptibility in bacteria with ARGs plasmids can be restored.This can limit the spread of antibiotic resistance.Additionally,it is essential to conduct experiments under a wide range of real-world environmental conditions.This will help to develop a novel approach for effectively addressing the antibiotic resistance crisis and the establishment of an all-around risk assessment system.

关 键 词：抗生素耐药基因 质粒 适应性代价 降低途径 

分 类 号：R446.5[医药卫生—诊断学]