Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS

Author:

Pérez-Vázquez María12,Sola Campoy Pedro J1,Ortega Adriana12,Bautista Verónica12,Monzón Sara3,Ruiz-Carrascoso Guillermo24,Mingorance Jesus24ORCID,González-Barberá Eva M5ORCID,Gimeno Concepción6,Aracil Belén12,Sáez David12,Lara Noelia12,Fernández Sara12,González-López Juan José27,Campos José12,Kingsley Robert A89,Dougan Gordon8,Oteo-Iglesias Jesús12ORCID,Rodrigo Cristina Herrera,Aznar Esteban,García-Picazo Luisa,Martínez Beatriz Orden,Mansilla Emilia Cercenado,Álvarez-García Patricia,Carretero Julia María Pita,Rodríguez-Conde Irene,Cao Sonia María Rey,Gimeno Adelina,Moreno Mar Olga Pérez,Rodríguez Ma Luz Cordón,Cavero Teresa Alarcón,Gil Yolanda,Esteras Ma Antonia Remacha,Andrés José Luis Barrios,Trujillo Gloria,Almaraz José Luis Hernández,José Luis del Pozo José Leiva León y,Salas Carmen Martín,Adán Fernando Buñuel,Bertomeu Frederic Gómez,Cascales Paloma,Dorado José Cobos,Suarez Concepción Balado,

Affiliation:

1. Laboratorio de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain

2. Spanish Network for Research in Infectious Diseases (REIPI RD12/0015 and REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain

3. Unidad de Bioinformátia (BU-ISCIII), Instituto de Salud Carlos III, Majadahonda, Madrid, Spain

4. Servicio de Microbiología, Hospital Universitario La Paz-idiPAZ, Madrid, Spain

5. Servicio de Microbiología, Hospital Universitario La Fe, Valencia, Spain

6. Servicio de Microbiología, Hospital General Universitario de Valencia, Valencia, Spain

7. Clinical Microbiology Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain

8. The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK

9. Quadram Institute Bioscience, Colney, Norwich, UK

Abstract

Abstract Objectives NDM carbapenemases have spread worldwide. However, little information exists about the impact of NDM-producing Enterobacteriaceae in Spain. By WGS, we sought to elucidate the population structure of NDM-like-producing Klebsiella pneumoniae and Escherichia coli in Spain and to determine the plasmids harbouring blaNDM-like genes. Methods High-resolution SNP typing, core-genome MLST and plasmid reconstruction (PlasmidID) were performed on 59 NDM-like-producing K. pneumoniae and 8 NDM-like-producing E. coli isolated over an 8 year period in Spain. Results Five major epidemic clones of NDM-producing K. pneumoniae caused five important nationwide outbreaks: ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1; in contrast, the spread of NDM-producing E. coli was polyclonal. Three blaNDM types were identified: blaNDM-1, 61.2%; blaNDM-7, 32.8%; and blaNDM-5, 6%. Five K. pneumoniae isolates co-produced other carbapenemases (three blaOXA-48 and two blaVIM-1). The average number of acquired resistance genes was higher in K. pneumoniae than in E. coli. The plasmids encoding blaNDM-like genes belonged to IncFII, IncFIB, IncX3, IncR, IncN and IncC types, of which IncF, IncR and IncC were associated with MDR. The genetic surroundings of blaNDM-like genes showed a highly variable region upstream of ISAba125. Conclusions In recent years NDM-producing K. pneumoniae and E. coli have emerged in Spain; the spread of a few high-risk K. pneumoniae clones such as ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1 have caused several interregional outbreaks. In contrast, the spread of NDM-producing E. coli has been polyclonal. Plasmid types IncFII, IncFIB, IncX3, IncR, IncN and IncC carried blaNDM, and the same IncX3 plasmid was detected in K. pneumoniae and E. coli.

Funder

European Development Regional Fund ERDF

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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