Whole genome sequencing, molecular typing and in vivo virulence of OXA-48-producing Escherichia coli isolates including ST131 H30-Rx, H22 and H41 subclones

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- fimH 30-virotype E; O25:H4-ST131/PST9- fimH 22-virotype D5, O16:H5-ST131/PST506- fimH 41; 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 bla OXA-48 gene was located in MOB P131 /IncL plasmids (four isolates) or within the chromosome (three ST131 H 30-Rx isolates), carried by Tn 1999 -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 bla OXA-48 -positive ST131, ST58 and ST83 E . coli isolates in conjunction with experimental data, and to evaluate the in vivo virulence of bla OXA-48 isolates, which pose an important challenge to patient management.