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Background <p>The spread of OXA-48-like carbapenemases represents a major public health challenge. Although previous studies have investigated OXA-48-like carbapenemases risk factors, nosocomial dissemination, and plasmid dynamics, an integrated plasmid-centered framework combining complete plasmid mining, transmission-unit analysis, phylogenetic reconstruction, and machine learning–based risk assessment remains limited.</p> Methods <p>We systematically collected 747 complete plasmid sequences carrying&#xa0;<i>bla</i><sub><i>OXA-48-like</i></sub> genes from the NCBI database, establishing the largest collections of complete plasmid sequences to date. Using an integrative framework of population genomics, phylogenetic dating, and machine learning, this study aimed to characterize the dissemination patterns, plasmid replicon diversity, transmission units, mobile genetic elements, co-resistance profiles, and risk classification of these plasmid.</p> Results <p>Plasmids carrying&#xa0;<i>bla</i><sub><i>OXA-48-like</i></sub> genes&#xa0;were detected across 50 countries on six continents, with <i>bla</i><sub><i>OXA-48</i></sub> predominating in Europe, <i>bla</i><sub><i>OXA-181</i></sub> in South Asia, and <i>bla</i><sub><i>OXA-232</i></sub> largely in Asia. IncL and ColKP3/IncX3 replicons, together with Tn1999.2 and other MGEs, were central drivers of plasmid maintenance and spread. Sixteen transmission units were defined, with AA068_Cluster3 estimated to have originated in the Netherlands around 2005 before expanding to Europe, the Middle East, Asia, and North America. Co-resistance analyses revealed frequent modules involving aminoglycoside and quinolone resistance, with <i>qnrS1</i> and <i>aph(3’’)-Ib</i> most prevalent. Notably, high-risk transposon structures were often identified in non-clinical environments, underscoring their cross-ecological transmission potential. Machine learning-based classification models showed good internal performance for predefined composite-risk categories, with plasmid mobility, clinical/non-clinical source composition, and host background contributing to the classification results.</p> Conclusions <p>This study provides a large-scale plasmid-centered genomic analysis of publicly available complete plasmid sequences carrying&#xa0;<i>bla</i><sub><i>OXA-48-like</i></sub> genes, integrating transmission-unit inference, phylogeographic reconstruction, mobile genetic element and co-resistance profiling, and composite genomic risk stratification. This gene-centered framework may support future One Health–oriented antimicrobial resistance surveillance and prioritization of plasmids with higher dissemination and resistance potential.</p>

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Spatiotemporal genomic analysis and risk assessment of the plasmids carrying blaOXA-48-like genes based on a large-scale international dataset

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月27日

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  • Qiheng Yuan,
  • Junlin Wang,
  • Xiaowei Liu,
  • Xumeng Yu,
  • Jiatao Li,
  • Du Guo,
  • Qinru Jing,
  • Yongliang Lou,
  • Yutong Kang,
  • Meiqin Zheng

摘要

Background

The spread of OXA-48-like carbapenemases represents a major public health challenge. Although previous studies have investigated OXA-48-like carbapenemases risk factors, nosocomial dissemination, and plasmid dynamics, an integrated plasmid-centered framework combining complete plasmid mining, transmission-unit analysis, phylogenetic reconstruction, and machine learning–based risk assessment remains limited.

Methods

We systematically collected 747 complete plasmid sequences carrying blaOXA-48-like genes from the NCBI database, establishing the largest collections of complete plasmid sequences to date. Using an integrative framework of population genomics, phylogenetic dating, and machine learning, this study aimed to characterize the dissemination patterns, plasmid replicon diversity, transmission units, mobile genetic elements, co-resistance profiles, and risk classification of these plasmid.

Results

Plasmids carrying blaOXA-48-like genes were detected across 50 countries on six continents, with blaOXA-48 predominating in Europe, blaOXA-181 in South Asia, and blaOXA-232 largely in Asia. IncL and ColKP3/IncX3 replicons, together with Tn1999.2 and other MGEs, were central drivers of plasmid maintenance and spread. Sixteen transmission units were defined, with AA068_Cluster3 estimated to have originated in the Netherlands around 2005 before expanding to Europe, the Middle East, Asia, and North America. Co-resistance analyses revealed frequent modules involving aminoglycoside and quinolone resistance, with qnrS1 and aph(3’’)-Ib most prevalent. Notably, high-risk transposon structures were often identified in non-clinical environments, underscoring their cross-ecological transmission potential. Machine learning-based classification models showed good internal performance for predefined composite-risk categories, with plasmid mobility, clinical/non-clinical source composition, and host background contributing to the classification results.

Conclusions

This study provides a large-scale plasmid-centered genomic analysis of publicly available complete plasmid sequences carrying blaOXA-48-like genes, integrating transmission-unit inference, phylogeographic reconstruction, mobile genetic element and co-resistance profiling, and composite genomic risk stratification. This gene-centered framework may support future One Health–oriented antimicrobial resistance surveillance and prioritization of plasmids with higher dissemination and resistance potential.