Abstract: Carbapenem-resistant Enterobacteriaceae, including the increasingly reported OXA-48 Escherichia
coli producers, are an emerging public health threat worldwide. Due to their alarming detection
in our healthcare setting and their possible presence in the community, seven OXA-48-producing,
extraintestinal pathogenic E. coli were analysed by whole genome sequencing as well as conventional
tools, and tested for in vivo virulence. As a result, five E. coli OXA-48-producing subclones were detected
(O25:H4-ST131/PST43-fimH30-virotype E; O25:H4-ST131/PST9-fimH22-virotype D5, O16:H5-ST131/
PST506-fimH41; O25:H5-ST83/PST207 and O9:H25-ST58/PST24). Four ST131 and one ST83 isolates
satisfied the ExPEC status, and all except the O16:H5 ST131 isolate were UPEC. All isolates exhibited
local inflammatory response with extensive subcutaneous necrosis but low lethality when tested in a
mouse sepsis model. The blaOXA-48 gene was located in MOBP131/IncL plasmids (four isolates) or within
the chromosome (three ST131 H30-Rx isolates), carried by Tn1999-like elements. All, except the ST83
isolate, were multidrug-resistant, with additional plasmids acting as vehicles for the spread of various
resistance genes. This is the first study to analyse the whole genome sequences of blaOXA-48-positive
ST131, ST58 and ST83 E. coli isolates in conjunction with experimental data, and to evaluate the in vivo
virulence of blaOXA-48 isolates, which pose an important challenge to patient management.