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.
Highlights
Escherichia coli is a common member of the intestine microbiota of warm-blooded vertebrates including humans
Virotypeg Phylogroup nt Origin, resistance properties and molecular typing of OXA-48 β-Lactamase Escherichia coli isolates from a Spanish hospital. aF, female; M, male. byears old. cGSU, general surgery unit-HUCA; ICU, intensive care unit-HUCA; RU, reanimation unit-HUCA; PCC, primary-care center; EU, emergency unit-HUCA; GU, geriatric unit of a long-term care facility; HUCA, Hospital Universitario Central de Asturias. dAMP, ampicillin; AMC, amoxicillin-clavulanic acid; FOX, cefoxitin; CTX, cefotaxime; ETP, ertapenem; IMP, imipenem; MER, meropenem; CHL, chloramphenicol, AMK, amikacin; GEN, gentamicin; KAN, kanamycin; TOB, tobramycin; STR, streptomycin, ERY, erythromycin; NAL, nalidixic acid; CIP, ciprofloxacin; SUL, sulfonamides; TMP, trimethoprim; SXT, trimethoprim-sulfamethoxazole; TET, tetracycline; I, intermediate resistance. eAll resistance genes were in silico determined; blaCTX-M-15 and blaOXA-48 were experimentally detected by PCR amplification
Plasmid genes are underlined. fST, sequence type according to Achtman; PST, sequence type according to the Pasteur Institute. gThe virotype was determined by PCR based on the presence or absence of 13 virulence genes[33]; nt, not typeable; na, not applicable. hIsolates partially characterized in a previous study15. iMIC of erythromycin: 256 μg/ml, higher than that obtained for isolates lacking mph(A): 128 μg/ml (Ec-HUCA 3, Ec-HUCA 5, Ec-HUCA 6, Ec-HUCA 7) or 64 μg/ml (Ec-HUCA 4)
Summary
Escherichia coli is a common member of the intestine microbiota of warm-blooded vertebrates including humans. Due to the alarming emergence of OXA-48-producing E. coli in our healthcare area, this study aimed to (i) analyse the genomic diversity of the isolates, using a combination of whole genome sequencing and molecular typing; (ii) investigate the role of plasmids in the dissemination of resistance and virulence genes, and (iii) assess the lethality of the isolates using a mouse sepsis model. For this purpose, seven OXA-48-producing E. coli recovered between 2012 and 2015 from clinical samples in three different settings within a Spanish city (Oviedo), were selected (Table 1)
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