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.
Bibliographical noteFunding Information:
This work was supported by the Instituto de Salud Carlos III of Spain (www.isciii.es) with the grant PI13/02092; and Spanish Network for Research in Infectious Diseases or REIPI (www.reipi.org): 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: email@example.com.