Zhong Yu-Xia, Cai Guijun, Dai Li-Ting, Yang Ling, Chen Ding-Qiang, Yuan Pei-Bo
Guangdong Provincial Clinical Research Center for Laboratory Medicine, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.
J Glob Antimicrob Resist. 2025 Aug 26. doi: 10.1016/j.jgar.2025.08.013.
Multidrug-resistant (MDR) Pseudomonas aeruginosa, especially carbapenemase-producing strains, poses major clinical challenges due to their widespread dissemination and limited treatment options.
A 65-year-old patient with intracranial infection was hospitalized. An MDR P. aeruginosa strain isolated from her cerebrospinal fluid was analyzed using MALDI-TOF mass spectrometry, antimicrobial susceptibility testing (AST), and whole genome sequencing (WGS).
P. aeruginosa strain YB1 was resistant to carbapenems, cephalosporins, quinolones, and aminoglycosides, except colistin. Its genome comprised a 6.41-Mb chromosome and a 448-kb IncP-like plasmid. Six β-lactamase genes were identified on the chromosome: bla, bla, bla, and bla in the MDR region, with bla and bla located outside it. The chromosomal MDR region shared high homology with plasmid-borne Tn6485e, which originated from multiple plasmids. Specifically, the novel carbapenemase gene bla resided in a conserved transposon (ISCR27n3-groL-△floR-bla-ble-trpF-ISCR27n2), identical to that originally characterized in the Alcaligenes faecalis plasmid. Additionally, bla was located in a conserved type I integron (IntI-aac(6')-Ib-bla-bla-catB3-△qacE-sul1). Notably, the 3'-terminal sequence of Tn6485e (IS26-aph(3')-Ia-IS26-tet(C)-tetR(C)-IS26-IS6100), absent from the chromosomal MDR region, was found on YB1's plasmid. Moreover, IS26 flanked the 71,600-bp chromosomal fragment covering the MRD region, with a 14-bp inverted repeat (5'-GGCACTGTTGCAAA-3') on their outer sides in the same orientation, implying potential IS26-facilitated plasmid-chromosome recombination.
This study first identified the coexistence of the bla and bla genes on the chromosome of P. aeruginosa. Monitoring gene transfer from plasmids to chromosomes is crucial, as it boosts bacterial survival against antibiotics and enables heritable resistance, threatening human health.
多重耐药（MDR）铜绿假单胞菌，尤其是产碳青霉烯酶菌株，因其广泛传播和治疗选择有限而带来重大临床挑战。
一名65岁颅内感染患者住院。对从其脑脊液中分离出的一株多重耐药铜绿假单胞菌菌株进行了基质辅助激光解吸电离飞行时间质谱分析、药敏试验（AST）和全基因组测序（WGS）。
铜绿假单胞菌菌株YB1对碳青霉烯类、头孢菌素类、喹诺酮类和氨基糖苷类耐药，但对黏菌素敏感。其基因组由一条6.41 Mb的染色体和一个448 kb的IncP样质粒组成。在染色体上鉴定出6个β-内酰胺酶基因：多重耐药区域中的bla、bla、bla和bla，bla和bla位于该区域之外。染色体多重耐药区域与源自多个质粒的质粒携带的Tn6485e具有高度同源性。具体而言，新型碳青霉烯酶基因bla位于一个保守转座子（ISCR27n3-groL-△floR-bla-ble-trpF-ISCR27n2）中，与最初在粪产碱杆菌质粒中鉴定的转座子相同。此外，bla位于一个保守的I型整合子（IntI-aac(6')-Ib-bla-bla-catB3-△qacE-sul1）中。值得注意的是，在YB1的质粒上发现了Tn6485e的3'末端序列（IS26-aph(3')-Ia-IS26-tet(C)-tetR(C)-IS26-IS6100），而该序列在染色体多重耐药区域中不存在。此外，IS26位于覆盖MRD区域的71,600 bp染色体片段两侧，其外侧有一个14 bp的反向重复序列（5'-GGCACTGTTGCAAA-3'），方向相同，这意味着可能存在IS26促进的质粒-染色体重组。
本研究首次在铜绿假单胞菌染色体上鉴定出bla和bla基因共存。监测基因从质粒向染色体的转移至关重要，因为这会增强细菌对抗生素的生存能力并产生可遗传的耐药性，威胁人类健康。
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