Department of Infectious Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.
Front Cell Infect Microbiol. 2021 Oct 25;11:757470. doi: 10.3389/fcimb.2021.757470. eCollection 2021.
can cause both hospital- and community-acquired clinical infections. Last-line antibiotics against carbapenem-resistant (CRKP), such as ceftazidime/avibactam (CZA) and tigecycline (TGC), remain limited as treatment choices. This study aimed to investigate the mechanisms by which CRKP acquires CZA and TGC resistance under β-lactam antibiotic and TGC exposure. Three CRKP strains (XDX16, XDX31 and XDX51) were consecutively isolated from an inpatient with a urinary tract infection in two months. PFGE and MLST showed that these strains were closely related and belonged to sequence type (ST) 4496, which is a novel ST closely related to ST11. Compared to XDX16 and XDX31, XDX51 developed CZA and TGC resistance. Sequencing showed that double copies of were located on a 108 kb IncFII plasmid, increasing expression in XDX51. In addition, was interrupted by Insertion sequence (IS) Kpn14 in XDX51, with this strain exhibiting upregulation of , and expression compared with XDX16 and XDX31. Furthermore, LPS analysis suggested that the O-antigen in XDX51 was defective due to IS insertion in the rhamnosyl transferase gene , which slightly reduced TGC susceptibility. In brief, CZA resistance was caused mainly by duplication, and TGC resistance was caused by inactivation with additional LPS changes due to IS element insertion in . Notably, CRKP developed TGC and CZA resistance within one month under TGC and β-lactam treatment without exposure to CZA. The CRKP clone ST4496 has the ability to evolve CZA and TGC resistance rapidly, posing a potential threat to inpatients during antibiotic treatment.
可导致医院获得性和社区获得性临床感染。针对耐碳青霉烯肠杆菌科细菌（CRKP）的最后一线抗生素，如头孢他啶/阿维巴坦（CZA）和替加环素（TGC），作为治疗选择仍然有限。本研究旨在探讨 CRKP 在β-内酰胺类抗生素和 TGC 暴露下获得 CZA 和 TGC 耐药性的机制。连续从一名在两个月内发生尿路感染的住院患者中分离出三株 CRKP 菌株（XDX16、XDX31 和 XDX51）。PFGE 和 MLST 表明这些菌株密切相关，属于序列型（ST）4496，这是一种与 ST11 密切相关的新型 ST。与 XDX16 和 XDX31 相比，XDX51 产生了 CZA 和 TGC 耐药性。测序表明， 位于一个 108kb IncFII 质粒上的两个拷贝，增加了 XDX51 中 的表达。此外，在 XDX51 中， 被插入序列（IS）Kpn14 打断，与 XDX16 和 XDX31 相比，该菌株 、 和 的表达上调。此外，LPS 分析表明，由于插入到 rhamnosyl 转移酶基因 中的 IS，XDX51 中的 O-抗原有缺陷，这略微降低了 TGC 的敏感性。总之，CZA 耐药性主要由 重复引起，TGC 耐药性是由 失活引起的，由于 IS 元件插入到 中，导致 LPS 发生变化。值得注意的是，CRKP 在没有暴露于 CZA 的情况下，在 TGC 和β-内酰胺治疗一个月内就产生了 TGC 和 CZA 耐药性。CRKP 克隆 ST4496 具有快速产生 CZA 和 TGC 耐药性的能力，这对接受抗生素治疗的住院患者构成了潜在威胁。
