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

Vanessa Koh, Rodrigo Cabrera, Prakki Sai Rama Sridatta, Natascha May Thevasagayam, Ze Qin Lim, Kalisvar Marimuthu, Indumathi Venkatachalam, Benjamin Pei Zhi Cherng, Raymond Kok Choon Fong, Surinder Kaur Pada, Say Tat Ooi, Nares Smitasin, Koh Cheng Thoon, Li Yang Hsu, Tse Hsien Koh, Partha Pratim De, Thean Yen Tan, Douglas Chan, Rama Narayana Deepak, Nancy Wen Sim Tee, Yunn-Hwen Gan, William Matlock, David W. Eyre, Michelle Ang, Raymond Tzer Pin Lin, Jeanette Teo and Oon Tek Ng ()
Additional contact information
Vanessa Koh: National Centre for Infectious Diseases
Rodrigo Cabrera: Universidad Del Rosario
Prakki Sai Rama Sridatta: National Centre for Infectious Diseases
Natascha May Thevasagayam: National Centre for Infectious Diseases
Ze Qin Lim: National Centre for Infectious Diseases
Kalisvar Marimuthu: National Centre for Infectious Diseases
Indumathi Venkatachalam: Singapore General Hospital
Benjamin Pei Zhi Cherng: National University of Singapore and National University Health System
Raymond Kok Choon Fong: Changi General Hospital
Surinder Kaur Pada: Ng Teng Fong General Hospital
Say Tat Ooi: Khoo Teck Puat Hospital
Nares Smitasin: National University of Singapore and National University Health System
Koh Cheng Thoon: KK Women’s and Children’s Hospital
Li Yang Hsu: National University of Singapore and National University Health System
Tse Hsien Koh: Singapore General Hospital
Partha Pratim De: Tan Tock Seng Hospital
Thean Yen Tan: Changi General Hospital
Douglas Chan: Ng Teng Fong General Hospital
Rama Narayana Deepak: Khoo Teck Puat Hospital
Nancy Wen Sim Tee: National University Hospital and National University Health System
Yunn-Hwen Gan: National University of
William Matlock: University of Oxford
David W. Eyre: University of Oxford
Michelle Ang: National Centre for Infectious Diseases
Raymond Tzer Pin Lin: National University Hospital and National University Health System
Jeanette Teo: National University Hospital and National University Health System
Oon Tek Ng: National Centre for Infectious Diseases

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-64515-7

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