Plasmid dynamics driving carbapenemase gene dissemination in healthcare environments: a nationwide analysis of closed Enterobacterales genomes

Thesis author

Benjamin Pei Zhi Cherng
David W. Eyre
Douglas Chan
Indumathi Venkatachalam
Jeanette Teo
Kalisvar Marimuthu
Koh Cheng Thoon
Li Yang Hsu
Michelle Ang
Nancy Wen Sim Tee
Nares Smitasin
Natascha May Thevasagayam
None None
Oon Tek Ng
Partha Pratim De
Prakki Sai Rama Sridatta
Rama Narayana Deepak
Raymond Kok Choon Fong
Raymond Tzer Pin Lin
Say Tat Ooi
Surinder Kaur Pada
Thean Yen Tan
Tse Hsien Koh
Vanessa Koh
William Matlock
Yunn Hwen Gan
Ze Qin Lim

Resumen

Plasmid-mediated transmission can account for half of carbapenem-producing Enterobacterales (CPE) dissemination, underscoring the need to identify genetic determinants of plasmid persistence in the hospital setting. From 1,088 CPE isolates detected through nationwide surveillance in Singapore over five years, 1,115 closed carbapenemase-producing plasmids were identified and clustered, of which 92.5% (n = 1031) were grouped into 48 plasmid clusters (PCs). The most common plasmid genotypes were PC1 and PC2. Of 389 isolates carrying blaKPC-2-positive PC1 plasmids and 283 isolates carrying blaNDM-1-positive PC2 plasmids, 236 (60.7%) and 168 (59.4%) putatively acquired the carbapenemase gene via plasmid-mediated horizontal transmission, whereas 153 (39.3%) and 115 (40.6%) putatively acquired the carbapenemase gene via clonal lineage-dependent vertical transmission, respectively. Less abundant plasmids showed distinct inserted genomic regions encoding genes related to heavy metal and formaldehyde detoxification not found in predominant plasmids. Our data suggest that PC1 and PC2 genotypes are better adapted for stable propagation of blaKPC-2 and blaNDM-1, respectively, during inter-patient clonal spread and across multiple species (and sequence types) compared to other genetic settings. We propose that a crucial factor enabling evolutionarily successful carbapenemase plasmid genotypes to achieve hyperendemicity in the population is the maintenance of conserved genomes, thus minimizing fitness costs to their hosts.

autores

http://vivoweb.org/ontology/core#FacultyMember
Cabrera Pérez, Rodrigo

fecha de publicación

2025-10-28

Edición

Número Internacional Normalizado de Publicaciones Seriadas (ISSN)

2041-1723

Identificador de objeto digital (DOI)

https://doi.org/10.1038/s41467-025-64515-7

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9522

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Plasmid dynamics driving carbapenemase gene dissemination in healthcare environments: a nationwide analysis of closed Enterobacterales genomes Artículo académico

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Número Internacional Normalizado de Publicaciones Seriadas (ISSN)

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