摘要
回顾性分析临床分离的1株同时产新德里金属-β-内酰胺酶(NDM)-1和亚胺培南水解β-内酰胺酶(IMP)-4碳青霉烯酶肺炎克雷伯菌KP1050,采用微量肉汤稀释法测定抗菌药物的最低抑菌浓度,全基因组测序确定菌株所携带耐药基因和耐药质粒。采用接合试验及基因敲除,明确耐药质粒的水平传播机制。肺炎克雷伯菌KP1050对包括碳青霉烯在内多种抗菌药物耐药,仅对阿米卡星、替加环素和多黏菌素敏感。该菌株为ST1245型,携带的bla_(NDM-1)和bla_(IMP-4)碳青霉烯酶耐药基因分别位于59730 bp的IncN型和289270 bp的IncHI5型质粒上。IncN和IncHI5型质粒均有完整的Ⅳ型分泌系统编码基因簇,也均可接合至受体菌,但IncN型NDM-1质粒的接合效率(1×10^(-3))高于IncHI5型IMP-4质粒(5×10^(-6))。对质粒Ⅳ型分泌系统关键基因的敲除发现,IncHI5型IMP-4质粒不是独立的可接合质粒,但可在IncN型NDM-1质粒的协助下通过接合进行水平传播。质粒间相互作用可促进碳青霉烯酶耐药基因的扩散。
A retrospective analysis was conducted on a clinically isolated Klebsiella pneumoniae strain KP1050 that produces both New Delhi Metallo-β-lactamase(NDM)-1 and Imipenem-hydrolyzingβ-lactamase(IMP)-4 carbapenemases.The minimum inhibitory concentrations of various antimicrobial agents were determined using the microbroth dilution method.Whole-genome sequencing was performed to identify the resistance genes and resistance plasmids carried by the strain.Conjugation assays and gene knockout techniques were employed to clarify the mechanisms of horizontal transfer of resistance plasmids.Klebsiella pneumoniae KP1050 was resistant to multiple antimicrobial agents,including carbapenems,and only susceptible to amikacin,tigecycline,and polymyxin.The strain belonged to ST1245,carrying the bla_(NDM-1)and bla_(IMP-4)carbapenemase resistance genes on the 59730 bp IncN-type and 289270 bp IncHI5-type plasmids,respectively.Both IncN and IncHI5-type plasmids harbored complete gene clusters encoding the typeⅣsecretion system and could be conjugated to recipient bacteria;however,the conjugation efficiency of the IncN-type NDM-1 plasmid(1×10⁻³)was higher than that of the IncHI5-type IMP-4 plasmid(5×10⁻⁶).Knockout of key genes in the plasmid typeⅣsecretion system revealed that the IncHI5-type IMP-4 plasmid was not an independently conjugative plasmid but could undergo horizontal transmission through conjugation with the assistance of the IncN-type NDM-1 plasmid.Interactions between plasmids can promote the spread of carbapenemase resistance genes.
作者
王晨
秦娟秀
李敏
沈震
Wang Chen;Qin Juanxiu;Li Min;Shen Zhen(Department of Laboratory Medicine,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)
出处
《中华医学杂志》
北大核心
2025年第34期3013-3016,共4页
National Medical Journal of China
基金
国家自然科学基金(82272374)。
关键词
克雷伯菌
肺炎
碳青霉烯类
质粒
接合
Klebsiella pneumoniae
Carbapenems
Plasmids
Conjugation
