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Longjie Zhou

Publications and source records attributed to Longjie Zhou.

2 recordsLinked to original sources

Genomic epidemiology and ceftazidime-avibactam resistance mechanism of KPC-3-producing Pseudomonas aeruginosa: A decade retrospective study in China.

OBJECTIVES: Carbapenem-resistant Pseudomonas aeruginosa (CRPA), especially KPC-producing P. aeruginosa, is rapidly expanding and posing a serious public health threat. Here, we aim to characterise the epidemiology of KPC-3-producing P. aeruginosa in a tertiary hospital over a 10-year period and elucidate the mechanism of ceftazidime-avibactam (CZA) resistance driven by blaKPC-3 to blaKPC-267 mutations in CRPA, along with conducting a global phylogeographic analysis of KPC-3-producing P. aeruginosa. METHODS: 11 non-duplicate KPC-3-producing CRPA isolates collected over a 10-year period were characterized by antimicrobial susceptibility testing and whole-genome sequencing (WGS). The genetic context and transferability of blaKPC-3/267 and the mechanism of KPC-267-mediated CZA resistance were investigated. Global phylogenomic analysis was performed to characterize the geographic distribution and population structure of blaKPC-3-carrying P. aeruginosa. RESULTS: All 11 KPC-3-producing CRPA strains in this study belonged to ST1076 and exhibited multidrug resistance. The blaKPC-267-positive CZA-resistant strain SRMPA3523 was isolated from patient 1 after blaKPC-3-positive P. aeruginosa SRMPA1139 and SRMPA1630 were treated with CZA. WGS indicated that blaKPC-3/267 was located on the Tn6296 transposon contained in the transferable IncP-2 plasmid. KPC-267 mediates resistance to CZA by reducing the inhibitory effect of avibactam and increasing affinity for ceftazidime. Global analysis indicated that blaKPC-3-carrying P. aeruginosa were predominantly in China, America, and Colombia, with ST1076 and ST111 as dominant clones. CONCLUSIONS: This study characterised the global phylogeography of blaKPC-3-carrying P. aeruginosa and identified KPC-267 as a KPC-3-derived variant associated with CZA resistance. This finding highlighted the risk of developing CZA resistance in KPC-producing P. aeruginosa strains under therapeutic pressure.

CRPA

Global emergence and transmission dynamics of carbapenemase-producing Citrobacter freundii sequence type 22 high-risk international clone: a retrospective, genomic, epidemiological study.

BACKGROUND: Carbapenemase-producing Citrobacter (CPC) species have recently been recognised as emerging pathogens associated with nosocomial infections in humans. The increased rate of Citrobacter freundii infections is a public health concern and there is a paucity of genomic data regarding its global transmission dynamics. We aimed to characterise the genetic features of CPC species, and their associated carbapenemase-encoding plasmids, obtained from hospitalised patients in China and from publicly available global data, with a particular focus on high-risk clones. METHODS: This was a retrospective, genomic epidemiological study of CPC species obtained from a tertiary hospital in Zhejiang Province, China, from March 5, 2013, to March 5, 2023. We used antimicrobial susceptibility testing, short-read and long-read whole-genome sequencing, phylogenomic analysis, and plasmid structure analysis. A global dataset of complete plasmid sequences encoding blaKPC, blaNDM, and blaIMP was constructed from the National Center for Biotechnology Information (NCBI) RefSeq database to provide insights into their diversity and distribution. All carbapenemase-producing Citrobacter freundii genomes from the NCBI GenBank database were incorporated in the comparative genomic analyses. Bayesian phylogeographical analysis and growth rate assays were carried out to characterise the high-risk C freundii sequence type (ST) 22 clone. FINDINGS: 1724 Citrobacter species isolates were collected from diverse clinical specimens, with 48 identified as CPC species. Citrobacter koseri (22 [46%] of 48) and C freundii (20 [42%]) were the predominant CPC species. Comparative analysis found C freundii carried significantly higher median numbers of plasmid replicons (5&#xb7;0 [IQR 3&#xb7;3-6&#xb7;0] vs 2&#xb7;0 [2&#xb7;0-3&#xb7;0]; p<0&#xb7;0001) and acquired antimicrobial resistance genes (12&#xb7;0 [7&#xb7;3-15&#xb7;8] vs 3&#xb7;0 [3&#xb7;0-5&#xb7;3]; p<0&#xb7;0001) than did C koseri. Molecular characterisation identified Inc-type plasmids, In823::Kl.pn.I3/In1589-like/In837-like integrons, Tn6296/Tn125/Tn5060 transposons, and insertion sequences (eg, IS26, IS3000, IS5, ISAba125, ISCR1), collectively facilitating the dissemination of carbapenemase genes. Global analysis of 3126 carbapenemase-encoding plasmids found epidemic plasmids with broad host ranges and global diversity. Phylogenetic investigation of predominant carbapenemase-encoding plasmids showed their persistence across geographical regions, temporal spans, and Enterobacterales species, exhibiting high genetic similarity to our clinical plasmids. A phylogenetic tree of 726 global carbapenemase-producing C freundii genomes showed that ST22 (227 [31&#xb7;3%]) represents the predominant multidrug-resistant clone across community, health-care, and environmental niches. Transmission across continents contributes to the global predominance of the ST22 clone, which carries a high load of resistance genes (median 15&#xb7;0 [IQR 11&#xb7;0-17&#xb7;0] vs 12&#xb7;0 [3&#xb7;0-16&#xb7;0]; p<0&#xb7;0001) and enhanced plasmid maintenance capacity (median replicons 5&#xb7;0 [IQR 4&#xb7;0-7&#xb7;0] vs 4&#xb7;0 [3&#xb7;0-6&#xb7;0]; p<0&#xb7;0001) relative to non-ST22 clones. INTERPRETATION: Our study provides evidence to suggest that Citrobacter species are emerging carriers of carbapenem-resistance genes. These findings provide insight into the population structure of CPC species and highlight C freundii ST22 as a prominent high-risk international clone. FUNDING: National Natural Science Foundation of China, National Health Commission Scientific Research Fund-Zhejiang Provincial Major Health Science and Technology Plan Project, Zhejiang Province Natural Science Foundation Project, Outstanding Youth Foundation of Jiangsu Province of China, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Postgraduate Research and Practice Innovation Program of Jiangsu Province.

Citrobacter freundii