Genomic differences between carbapenem-susceptible and carbapenem-resistant Escherichia coli analyzed by whole-genome sequencing

The widespread resistance to carbapenem via Enterobacteriaceae is a major public health concern. To investigate the reason for the change of Escherichia coli from carbapenem-susceptible to carbapenem-resistant status after antibiotic therapy, whole-genome sequencing was applied for the analysis of genetic difference between the two isolates. The genome of the two isolates of Escherichia coli with distinct resistant phenotypes recovered from one patient was sequenced and compared. Singlenucleotide polymorphisms and insertions/deletions were analyzed using software MUMmer (http://mummer.sourceforge.net/). The homology of chromosomes, plasmid 1, and plasmid 2 between the two isolates was very high (>99.5%). However, the coverage ratio of plasmid 3 was only 7.13%. This plasmid harbored the IMP-4 carbapenemase-coding gene. The upstream of blaIMP-4 was the plasmid mobilization relaxosome protein Mobe gene and the downstream were class 1 integrom integrase IntI1 and IS6 family transposase IS15DIV, which may be related to carbapenemase gene capture. Single-nucleotide mutation, insertion, and deletion could not result in the development of resistance to carbapenem, whereas acquisition of the IMP-4-encoding gene may be the reason for changes in resistance to carbapenem.