Whole-genome Sequences of Multidrug-Resistant Escherichia coli

Abstract

Escherichia coli is a common opportunistic Gram-negative organism and a member of the intestinal microflora. Its pathogenicity is associated with several disorders, such as urinary tract infections (UTI), pulmonary, intra-abdominal, skin, and soft tissue infections, and hemolytic uremic syndrome (HUS). Throughout the past years and because of increased resistance to Extended spectrum β-lactams and carbapenems, the World Health Organization (WHO) added it to the list of bacteria posing the greatest threat to human health. In this study, we performed a whole-genome sequence-based analysis to understand the molecular epidemiology of multidrug-resistant E. coli clinical isolates. Genome comparison, multilocus sequence typing (MLST), and whole-genome SNP-based phylogenetic analysis (wgSNP) were used to determine the relatedness of the isolates. In silico analysis was used to determine the resistance genes, virulence factors, Inc groups, and O and H serotypes. Antimicrobial phenotypic susceptibility tests showed that all the isolates were resistant to amoxicillin. At the same time, variable resistance patterns were detected for the other tested drugs, with resistance to fosfomycin, cefoxitin, and nitrofurantoin being reported. Most isolates showed resistance to at least one tested carbapenem, including imipenem, meropenem, and ertapenem. Genomic analysis of 19 representative isolates revealed the presence of several β-lactamases including blaCTX-M-15, blaOXA-181, blaNDM-1, blaNDM-5, blaNDM-6, and aminoglycoside resistance genes including aac(6′)-Ib-cr and aph(3’’)-Id. The most common Inc group detected was IncFIB, followed by IncFIA, with one isolate containing IncFII(Yp) harboring blaNDM-6. The isolates were distributed among different phylogroups groups: group A, 8 (42.1%), group B1, 2 (10.5%), group B2, 5 (26.3%), group C, 1 (5.2%), group D, 2 (10.5%), group F, 1 (5.2%). The studied isolates were distributed over 16 sequence types, with some, such as ST131, being linked to the global spread of antibiotic resistance. To our knowledge, this is the first detection of blaNDM-6 encoding E. coli from Lebanon. Our study revealed the diversity within E. coli clinical isolates and the role of mobile elements in disseminating resistance determinants. Whole-genome sequencing significantly enhanced infectious disease surveillance, our understanding of transmission dynamics, and the detection of antimicrobial resistance determinants.