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

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 bla<sub>KPC-2</sub>-positive PC1 plasmids and 283 isolates carrying bla<sub>NDM-1</sub>-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 bla<sub>KPC-2</sub> and bla<sub>NDM-1</sub>, 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.

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Journal
Nature Communications
Published
2025-10-28
DOI
https://doi.org/10.1038/s41467-025-64515-7
Citations
1
Primary Topic
Antibiotic Resistance in Bacteria
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article
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0.59
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article

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

Yunn‐Hwen Gan, Prakki Sai Rama Sridatta, Douglas Chan, Nancy Wen Sim Tee et al.
1 citations
Nature Communications
Antibiotic Resistance in Bacteria
0.59
article

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

Yunn‐Hwen Gan, Prakki Sai Rama Sridatta, Douglas Chan, Nancy Wen Sim Tee, Koh Cheng Thoon, Nares Smitasin, Rodrigo Cabrera, Michelle Ang, Tse Hsien Koh, Raymond Tzer Pin Lin, Oon Tek Ng, Indumathi Venkatachalam, Vanessa Koh, Benjamin Pei Zhi Cherng, Thean Yen Tan, Raymond Fong, David W. Eyre, Natascha May Thevasagayam, Jeanette Teo, Rama Narayana Deepak, Surinder Pada, William Matlock, Ze Qin Lim, Li Yang Hsu, Kalisvar Marimuthu, Say Tat Ooi, Partha Pratim De
article en
1 citations

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 bla<sub>KPC-2</sub>-positive PC1 plasmids and 283 isolates carrying bla<sub>NDM-1</sub>-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 bla<sub>KPC-2</sub> and bla<sub>NDM-1</sub>, 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.

Nature CommunicationsVol. 16(1)
National University of Singapore (SG), Nanyang Technological University (SG), Singapore General Hospital (SG), Changi General Hospital (SG), Tan Tock Seng Hospital (SG), Khoo Teck Puat Hospital (SG), Ng Teng Fong General Hospital (SG), University of Oxford (GB), KK Women's and Children's Hospital (SG), Duke-NUS Medical School (SG), Singapore Centre for Environmental Life Sciences Engineering (SG), National University Health System (SG), National Centre for Infectious Diseases (SG), Universidad del Rosario (CO)
Openalex Percentile: Top 29%
Antibiotic Resistance in Bacteria
0.59
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