@article{816b2156a6294ceb8103dade3abcd989,
title = "Dynamics of blaKPC-2 Dissemination from Non-CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity",
abstract = "Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/ colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene “epidemic” was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.",
keywords = "Bla, Colombia, Enterobacterales, IncN plasmid, Klebsiella pneumoniae non-CG258, Outbreak, Whole-genome sequencing",
author = "Rada, {Ana M.} and {de la Cadena}, Elsa and Carlos Agudelo and Cesar Capataz and Nataly Orozco and Cristian Pallares and Dinh, {An Q.} and Diana Panesso and Rafael R{\'i}os and Lorena Diaz and Adriana Correa and Hanson, {Blake M.} and Villegas, {Maria V.} and Arias, {Cesar A.} and Eliana Restrepo",
note = "Funding Information: We thank the Hospital San Juan de Dios, the Fundaci{\'o}n Cl{\'i}nica del Norte, and the Cl{\'i}nica Universitaria Bolivariana for providing clinical and microbiological information and sending isolates. This study was supported by funding (grant 1115-5693-3375) from the Colombian Agency for Science, Technology, and Innovation (COLCIENCIAS) (to E.R. and N.O.); Instituci{\'o}n Universitaria Colegio Mayor de Antioquia grant FCS46-2016 (to A.M.R.); NIH/National Institutes of Allergy and Infectious Diseases (NIAID) grants K24-AI121296 (C.A.A.), R01AI093749 (C.A.A.), and R01AI134637 (to C.A.A.); a University of Texas System Faculty Science and Technology Acquisition and Retention (STAR) Award (to C.A.A.); and a University of Texas Health Science Center at Houston Presidential Award (to C.A.A.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. C.A.A. has received grant support from Merck, Inc.; Entasis Pharmaceuticals; and MeMed. M.V.V. has received grant support from Merck, Inc.; Pfizer; and West Qu{\'i}mica. All other authors declare no conflicts of interest. Significant contributions to laboratory processing were made by E.D.C., N.O., D.P., and A.M.R. Collection and analysis of clinical data were done by C.A., C.C., and C.P. Short-read (Illumina) sequencing was performed by R.R., L.D., A.Q.D., and A.M.R. Long-read (MinION) sequencing was performed by B.M.H. Sequence data processing and analysis were performed by R.R., L.D., and A.M.R. A.M.R. and C.A.A. wrote the manuscript, which was reviewed by A.C., M.V.V., and E.R. Funding Information: This study was supported by funding (grant 1115-5693-3375) from the Colombian Agency for Science, Technology, and Innovation (COLCIENCIAS) (to E.R. and N.O.); Instituci{\'o}n Universitaria Colegio Mayor de Antioquia grant FCS46-2016 (to A.M.R.); Funding Information: NIH/National Institutes of Allergy and Infectious Diseases (NIAID) grants K24-AI121296 (C.A.A.), R01AI093749 (C.A.A.), and R01AI134637 (to C.A.A.); a University of Texas System Faculty Science and Technology Acquisition and Retention (STAR) Award (to C.A.A.); and a University of Texas Health Science Center at Houston Presidential Award (to C.A.A.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. C.A.A. has received grant support from Merck, Inc.; Entasis Pharmaceuticals; and MeMed. M.V.V. has received grant support from Merck, Inc.; Pfizer; and West Qu{\'i}mica. All other authors declare no conflicts of interest. Publisher Copyright: Copyright {\textcopyright} 2020 American Society for Microbiology. All Rights Reserved.",
year = "2020",
month = dec,
doi = "10.1128/AAC.01743-20",
language = "English (US)",
volume = "64",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "12",
}