Virulence genes and subclone status as markers of experimental virulence in a murine sepsis model among Escherichia coli sequence type 131 clinical isolates from Spain

Irene Merino, Stephen B. Porter, Brian D. Johnston, Connie Clabots, Evelyn Shaw, Juan Pablo Horcajada, Rafael Cantón, Patricia Ruiz-Garbajosa, James R. Johnson, ITUBRAS-GEIH group

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Objective: To assess experimental virulence among sequence type 131 (ST131) Escherichia coli bloodstream isolates in relation to virulence genotype and subclone. Methods: We analysed 48 Spanish ST131 bloodstream isolates (2010) by PCR for ST131 subclone status (H30Rx, H30 non-Rx, or non-H30), virulence genes (VGs), and O-type. Then we compared these traits with virulence in a murine sepsis model, as measured by illness severity score (ISS) and rapid lethality (mean ISS ≥ 4). Results: Of the 48 study isolates, 65% were H30Rx, 21% H30 non-Rx, and 15% non-H30; 44% produced ESBLs, 98% were O25b, and 83% qualified as extraintestinal pathogenic E. coli (ExPEC). Of 49 VGs, ibeA and iss were associated significantly with non-H30 isolates, and sat, iha and malX with H30 isolates. Median VG scores differed by subclone, i.e., 12 (H30Rx), 10 (H30 non-Rx), and 11 (non-H30) (p < 0.01). Nearly 80% of isolates represented a described virotype. In mice, H30Rx and non-H30 isolates were more virulent than H30 non-Rx isolates (according to ISS [p = 0.03] and rapid lethality [p = 0.03]), as were ExPEC isolates compared with non-ExPEC isolates (median ISS, 4.3 vs. 2.7: p = 0.03). In contrast, most individual VGs, VG scores, VG profiles, and virotypes were not associated with mouse virulence. Conclusions: ST131 subclone and ExPEC status, but not individual VGs, VG scores or profiles, or virotypes, predicted mouse virulence. Given the lower virulence of non-Rx H30 isolates, hyper-virulence probably cannot explain the ST131-H30 clade’s epidemic emergence.

Original languageEnglish (US)
Article numbere0188838
JournalPloS one
Issue number11
StatePublished - Nov 2017

Bibliographical note

Funding Information:
This work was supported by the Instituto de Salud Carlos III of Spain ( with the grant PI13/02092; and Spanish Network for Research in Infectious Diseases or REIPI ( RD12/0015/0004 and RD16/0016/0011; and co-financed by the European Development Regional Fund (ERDF), “A Way to Achieve Europe”. IMV is supported by a research contract from the REIPI (RD12/0015/0004). Part of this work was supported by a grant from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) (Ayuda a la formación de la SEIMC 2014, IMV). This material also is based partly upon work supported by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000192 01 (JRJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The ITUBRAS-GEIH group are: JP. Horcajada (Hospital del Mar, Barcelona, Spain); E. Shaw (Hospital Universitario de Bellvitge-IDIBELL, Barcelona, Spain); E. Bunshow, E. Cercenado, B. Padilla and C. Sánchez-Carrillo (Hospital Gregorio Marañón, Madrid, Spain); MC. Fariñas, M. Gonzalo and L. Martínez-Martínez (Hospital Marqués de Valdecilla, Santander, Spain); E. Calbo, M. Riera, and M. Xercavins (Hospital Universitario Mútua de Terrassa, Barcelona, Spain); R. Gamallo and MA. Pallarés (Complexo Hospitalario de Pontevedra, Pontevedra, Spain); R Cantón, P. Ruiz-Garbajosa, and V. Pintado (Hospital Universitario Ramón y Cajal, Madrid, Spain); J. Gomez (Laboratorio de Referencia de Cataluña, Barcelona, Spain); N. Benito and B. Mirelis (Hospital Santa Creu i Sant Pau, Barcelona, Spain); and M. de Cueto, A. Pascual and J. Rodríguez-Baño (Hospital Virgen Macarena, Sevilla, Spain). Lead autor of the ITU-BRAS group: Juan Pablo Horcajada, Hospital del Mar-Medical Research Institute of Hospital del Mar (IMIM)-CEXS, Universitat Pompeu Fabra, Barcelona, Spain. Contact email address:

Publisher Copyright:
© 2017 Merino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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