Abstract

Escherichia coli strain CCUG 78773 is a virulent extended-spectrum β-lactamase (ESBL)-producing ST131-O25b type strain isolated during an outbreak at a regional university hospital. The complete and closed genome sequence, comprising one chromosome (5,076,638 bp) and six plasmids (1718–161,372 bp), is presented. Characterization of the genomic features detected the presence of 59 potential antibiotic resistance factors, including three prevalent β-lactamases. Several virulence associated elements were determined, mainly related with adherence, invasion, biofilm formation and antiphagocytosis. Twenty-eight putative type II toxin-antitoxin systems were found. The plasmids were characterized, through in silico analyses, confirming the two β-lactamase-encoding plasmids to be conjugative, while the remaining plasmids were mobilizable. BLAST analysis of the plasmid sequences showed high similarity with plasmids in E. coli from around the world. Expression of many of the described virulence and AMR factors was confirmed by proteomic analyses, using bottom-up, liquid chromatography-tandem mass spectrometry (LC-MS/MS). The detailed characterization of E. coli strain CCUG 78773 provides a reference for the relevance of genetic elements, as well as the characterization of antibiotic resistance and the spread of bacteria harboring ESBL genes in the hospital environment.

Highlights

  • Extended-spectrum β-lactamases (ESBLs) are enzymes able to hydrolyze and inactivate clinically-relevant β-lactam antibiotics, such as penicillins, cephalosporins and monobactams [1]

  • E. coli strain Collection University of Gothenburg (CCUG) 73778 was originally isolated from blood, it was shown to be closely related to other isolates from the same outbreak which had been obtained from urine and feces samples of other infants [14]

  • Plasmid sequences from isolates from around the world, with high similarities to the plasmids of E. coli strain CCUG 73778, were found in the nucleic acid sequence databases, exemplifying the global problem of transmission of resistance genes through mobility of plasmids

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Summary

Introduction

Extended-spectrum β-lactamases (ESBLs) are enzymes able to hydrolyze and inactivate clinically-relevant β-lactam antibiotics, such as penicillins, cephalosporins and monobactams [1]. Propagation of ESBL genes among bacteria has been reported worldwide, representing a global problem for human health [3,4,5]. Members of the family Enterobacteriaceae, such as Escherichia coli, harboring ESBL genes represent an increasingly important threat for human health [6]. Infections caused by ESBL-producing E. coli (ESBL-E. coli), or any other ESBL-producing Enterobacteriaceae, extend patient morbidity, mortality and length of stay at hospitals, imparting significant economic burdens to the health care system. For these reasons and to prevent transmission of resistance and outbreaks caused by these bacteria, the study and understanding of ESBL-producing bacteria is highly important [7]

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