Circulation of emerging NDM-5-producing Escherichia coli among humans and dogs in Egypt

Authors: RAMADAN, HAZEM - Mansoura University; GUPTA, SUSHIM - Orise Fellow; SHARMA, POONAM - Orise Fellow; AHMED, MARWA - Mansoura University; Hiott, Lari; Barrett, John; Woodley, Tiffanie; Frye, Jonathan; Jackson, Charlene

Submitted to: Zoonoses and Public Health
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/25/2019
Publication Date: 12/22/2019
Citation: Ramadan, H., Gupta, S., Sharma, P., Ahmed, M., Hiott, L.M., Barrett, J.B., Woodley, T.A., Frye, J.G., Jackson, C.R. 2019. Circulation of emerging NDM-5-producing Escherichia coli among humans and dogs in Egypt. Zoonoses and Public Health. https://doi.org/10.1111/zph.12676.
DOI: https://doi.org/10.1111/zph.12676

Interpretive Summary: The emergence of carbapenem-resistant Escherichia coli has considerably threatened human and animal health worldwide. In this study, the carbapenem-resistance gene, New Delhi Metalloprotease (NDM), and genetic relatedness of E. coli from humans and dogs in Egypt was investigated. Using whole genome sequencing (WGS), two different NDM variants were identified; blaNDM-5 in E. coli from urine of a healthy person and environmental samples of dogs, and blaNDM-1 in E. coli from a human patient’s urine. The NDM gene was associated with the same plasmid type in E. coli from both humans and dogs, but could not transfer to other E. coli by conjugation. This study showed, for the first time in Egypt, the emergence of blaNDM-5 E. coli in dogs that share similar genetic features with human E. coli in the same area. This study will be useful for regulatory agencies as it shows that periodic surveillance and monitoring of emerging antimicrobial resistance using WGS are warranted for setting control interventions.

Technical Abstract: The emergence of New Delhi Metalloprotease (NDM)-producing Escherichia coli has considerably threatened human and animal health worldwide. This study describes for the first time in Egypt, the draft genome sequences of emerging NDM-5-producing E. coli from humans and dogs, and investigates genetic relatedness between isolates from both sources. Two E. coli from human urine and seven from environmental clinical samples of dogs exhibited resistance to carbapenems and harboring blaNDM were subjected to Illumina Miseq whole genome sequencing (WGS). Assembly and analysis of the reads were performed to identify resistance genes, multilocus sequence types (MLST), plasmid replicon types (Inc) and insertion sequences (IS) of the blaNDM region; core genome MLST (cgMLST) analysis was also performed. Two different NDM alleles were identified; blaNDM-5 in E. coli HR119 from the urine of a healthy person and environmental samples of dogs, and blaNDM-1 in E. coli HR135 from a human patient’s urine. Multiple mobilizable resistance genes to different antimicrobial classes were identified except the colistin resistance gene, mcr. E. coli isolates from humans and dogs were assigned to different sequence types (STs). Using cgMLST, dog isolates clustered together with only 1-2 allellic differences; however, human E. coli showed 1,978 different allelles compared with dog isolates. Plasmidfinder results indicated the presence of an IncX3 replicon in blaNDM-5-producing E. coli; however, blaNDM-1 was linked to IncCoIKP3. Notably, the NDM region (3 Kb) in all isolates from humans and dogs were highly similar with variable flanking sequences that represented different IS elements. This study reports the first emergence of NDM-5-producing E. coli from dogs in Egypt that shared some genetic features with human isolates, and could be considered potential public health threats.