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In vivo Emergence of Colistin and Tigecycline Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae During Antibiotics Treatment
Frontiers in Microbiology ( IF 5.2 ) Pub Date : 2021-09-16 , DOI: 10.3389/fmicb.2021.702956
Jiawei Chen 1 , Yu Zeng 1 , Rong Zhang 1 , Jiachang Cai 1
Affiliation  

Three carbapenem-resistant Klebsiella pneumoniae (CRKP; strains KP-426, KP-C76, and KP-CT77) were isolated from a patient with severe burns during the treatment of colistin and tigecycline. Single-nucleotide polymorphism typing showed that three ST11 CRKP were clonally related. Three isolates harbored the same set of antimicrobial resistance genes. blaKPC-2, blaSHV-12, blaTEM-1, and rmtB genes were located on the same 128,928-bp IncFII/IncR plasmid. Tet(A), catA2, sul2, and dfrA14 genes were located on a plasmid with an unknown Inc-type. blaSHV-11, fosA, and aadA2 were chromosomal genes. An IS1 and an ISKpn14 were found in the promoter region of the mgrB gene of two colistin-resistant CRKP, K. pneumoniae KP-C76, and KP-CT77, respectively. A novel amino acid substitution, G300E, was identified in the type 1 Tet(A) variant of K. pneumoniae KP-CT77 which exhibited high-level tigecycline resistance compared to strains KP-426 and KP-C76 (MIC of 32, 4, and 4mg/l, respectively). Conjugation and cloning experiments confirmed that the mutated Tet(A) resulted in a 4-fold increase in tigecycline minimal inhibitory concentration (MIC) of Escherichia coli. Three CRKP belonged to the K64 serotype and possessed a similar IncHI1B/repB virulence plasmid carrying rmpA, rmpA2, and iucABCDiutA. The survival rates of Galleria Mellonella injected with K. pneumoniae KP-426, KP-C76, and KP-CT77 were 4.2, 20.8, and 8.3%, respectively. The emergence of colistin and tigecycline resistance in carbapenem-resistant hypervirulent K. pneumoniae posed a serious threat to clinical anti-infective therapy. The type 1 Tet(A) variant carrying G300E mutation, which conferred significantly elevated tigecycline MIC and was located on a conjugative plasmid, needs attention.



中文翻译:

抗生素治疗期间耐碳青霉烯的高毒力肺炎克雷伯菌体内出现粘菌素和替加环素耐药性

三抗碳青霉烯类 肺炎克雷伯菌(CRKP;菌株 KP-426、KP-C76 和 KP-CT77)是从一名在粘菌素和替加环素治疗期间严重烧伤的患者中分离出来的。单核苷酸多态性分型显示三个 ST11 CRKP 是无性系相关的。三个分离株含有相同的抗菌素抗性基因组。布拉KPC-2 ,布拉SHV-12 ,布拉TEM-1乙肝 基因位于相同的 128,928 bp IncFII/IncR 质粒上。 春节(一种), 猫A2, sul2, 和 dfrA14 基因位于具有未知 Inc 型的质粒上。 布拉SHV-11 ,fosA, 和 aadA2是染色体基因。信息系统1 和一个 ISKPN14 在启动子区发现 管理人员B 两个抗粘菌素CRKP基因, 肺炎克雷伯菌分别为 KP-C76 和 KP-CT77。在 1 型 Tet(A) 变体中鉴定出一种新的氨基酸取代 G300E肺炎克雷伯菌与菌株 KP-426 和 KP-C76 相比,KP-CT77 表现出高水平的替加环素耐药性(MIC 分别为 32、4 和 4mg/l)。缀合和克隆实验证实突变的 Tet(A) 导致替加环素最小抑制浓度 (MIC) 增加 4 倍大肠杆菌. 三个CRKP属于K64血清型,具有相似的IncHI1B/repB毒力质粒携带rmpA, rmpA2, 和 iucABCDiutA. 的存活率梅隆内拉广场 注入 肺炎克雷伯菌KP-426、KP-C76 和 KP-CT77 分别为 4.2、20.8 和 8.3%。耐碳青霉烯类高毒株中粘菌素和替加环素耐药的出现肺炎克雷伯菌对临床抗感染治疗构成严重威胁。携带 G300E 突变的 1 型 Tet(A) 变体导致替加环素 MIC 显着升高并位于接合质粒上,需要注意。

更新日期:2021-09-16
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