Zhang Xiaodong, Tang Miran, Xu Ye, Xu Mengxin, Qian Changrui, Zheng Xiangkuo, Zhou Tieli, Wu Qing
Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, China.
Department of Clinical Laboratory, Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.
J Glob Antimicrob Resist. 2023 Mar;32:122-130. doi: 10.1016/j.jgar.2023.01.011. Epub 2023 Feb 16.
This study aimed to elucidate resistance to carbapenems and fluoroquinolones, the transmission mechanism of bla, and the virulence characteristics of a Pseudomonas aeruginosa strain (TL3773) isolated in East China.
The virulence and resistance mechanisms of TL3773 were investigated by whole genome sequencing (WGS), comparative genomic analysis, conjugation experiments, and virulence assays.
This study isolated carbapenem-resistant P. aeruginosa from blood resistant to carbapenems. The patient's clinical data showed poor prognosis compounded by multiple sites of infection. WGS showed that TL3773 carried aph (3')-IIb, bla, bla, fosA, catB7, and two crpP resistance genes on chromosome, and the carbapenem resistance gene bla on plasmid. We identified a novel crpP gene named TL3773-crpP2. Cloning experiments proved that TL3773-crpP2 was not the primary cause of fluoroquinolone resistance in TL3773. GyrA and ParC mutations may confer fluoroquinolone resistance. The bla genetic environment was IS26-TnpR-ISKpn27-bla-ISKpn6-IS26-Tn3-IS26, potentially mediating the transmission of bla in P. aeruginosa. The overall virulence of TL3773 was lower than that of PAO1. However, the pyocyanin and biofilm formation of TL3773 was higher than that of PAO1. WGS further indicated that TL3773 was less virulent than PAO1. Phylogenetic analysis showed that TL3773 was most similar to the P. aeruginosa isolate ZYPA29 from Hangzhou, China. These observations further indicate that ST463 P. aeruginosa is rapidly spreading.
The threat of ST463 P. aeruginosa harbouring bla is emergent and may pose a threat to human health. More extensive surveillance and effective actions are urgently needed to control its further spread.
本研究旨在阐明华东地区分离出的一株铜绿假单胞菌（TL3773）对碳青霉烯类和氟喹诺酮类的耐药性、bla的传播机制及其毒力特征。
通过全基因组测序（WGS）、比较基因组分析、接合实验和毒力测定研究TL3773的毒力和耐药机制。
本研究从对碳青霉烯类耐药的血液中分离出耐碳青霉烯类铜绿假单胞菌。患者的临床资料显示，由于多部位感染，预后较差。WGS显示，TL3773在染色体上携带aph(3')-IIb、bla、bla、fosA、catB7和两个crpP耐药基因，在质粒上携带碳青霉烯类耐药基因bla。我们鉴定出一个名为TL3773-crpP2的新型crpP基因。克隆实验证明，TL3773-crpP2不是TL3773对氟喹诺酮类耐药的主要原因。GyrA和ParC突变可能赋予对氟喹诺酮类的耐药性。bla的遗传环境为IS26-TnpR-ISKpn27-bla-ISKpn6-IS26-Tn3-IS26，可能介导bla在铜绿假单胞菌中的传播。TL3773的总体毒力低于PAO1。然而，TL3773的绿脓菌素和生物膜形成高于PAO1。WGS进一步表明，TL3773的毒力低于PAO1。系统发育分析表明，TL3773与来自中国杭州的铜绿假单胞菌分离株ZYPA29最相似。这些观察结果进一步表明，ST463铜绿假单胞菌正在迅速传播。
携带bla的ST463铜绿假单胞菌构成的威胁迫在眉睫，可能对人类健康构成威胁。迫切需要更广泛的监测和有效行动来控制其进一步传播。
