Vanessa Koh, Rodrigo Cabrera, Prakki Sai Rama Sridatta, Natascha May Thevasagayam, Ze Qin Lim, Kalisvar Marimuthu, Indumathi Venkatachalam, Benjamin Pei Zhi Cherng, Raymond Fong, Surinder 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, Oon Tek Ng, the Carbapenemase-Producing Enterobacteriaceae in Singapore (CaPES) Study Group
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. Plasmid-mediated transmission plays a significant role in the spread of carbapenem-resistant Enterobacterales. Here, analyzing 1,115 carbapenemase-producing plasmids from Singapore, the authors suggest that maintenance of conserved genomes adapted for stable propagation across multiple species, enables evolutionarily successful carbapenemase plasmid genotypes to achieve hyperendemicity in the population.