Comparative Genomics Revealed Fluoroquinolone Resistance Determinants and OmpF Deletion in Carbapenem-Resistant Escherichia coli

Abstract

Escherichia coli (E. coli) is a major causative organism of complicated urinary tract infections, bloodstream infections, and pneumonia. With the widespread use of antimicrobial agents, the prevalence of carbapenem resistance in E. coli has been increasing with limited therapeutic options. Fluoroquinolone remains a choice in carbapenem-resistant E. coli (CREc) that were once susceptible to the drug. Despite robust studies on the fluoroquinolone-resistant mechanisms of E. coli, few studies focused specifically on the group of CREc. In this study, we used comparative genomics to identify the fluoroquinolone-resistant mechanisms of CREc and detected gyrA D87N mutation in all the fluoroquinolone-resistant and CREc. Moreover, to investigate the mechanism underlying non-carbapenemase-producing carbapenem-resistant E. coli, we targeted the complete genome sequences for in-depth analysis and found a deletion in OmpF (DEL264-269) that might contribute to carbapenem resistance, which has not been reported before. Further studies focusing on the impact of these mutations on the expression levels are warranted. We further investigate the MLST, serotype, fimH type, phylogroup, and clinical characteristics of the CREc. Combination analysis of clinical and genomic characteristics suggests the polyclonal and highly diverse nature of the CREc in Taiwan. This study provides an insight into the molecular epidemiology of CREc in Taiwan.

Keywords: Escherichia coli; carbapenem-resistant; carbapenemase; epidemiology; virulence; whole-genome sequencing.

Figure 1

(A) Multiple sequence alignment of OmpF revealed deletion in 264-269. (B) Phylogenetic clusters in deleted OmpF.

Figure 2

Venn diagrams comparing virulence factors of bloodstream infections from abdominal origin or urologic origin. Five E. coli isolates from the urinary tract shared eight virulence factors, including gad, terC, traT, fyuA, irp2, iucC, iutA, and ompT. Five E. coli isolates from abdominal origin shared four virulence factors, including gad, terC, traT, and sitA. Bloodstream infection from both sources contained virulence factors of gad, terC, and traT. Venn diagrams were created by InteractiVenn (Heberle et al., 2015).

Figure 3

The reporting proportion of non-CP-CRE and carbapenemase among CREc/CNSEc (Rimrang et al., ; Del Franco et al., ; Lefebvre et al., ; Baran and Aksu, ; Dupont et al., ; Jeong et al., ; Sharma et al., ; Grundmann et al., ; Karlowsky et al., ; Marimuthu et al., ; Trepanier et al., ; Abd El Ghany et al., ; Dagher et al., ; Senchyna et al., ; Al-Farsi et al., ; Abid et al., ; Huang et al., ; Musila et al., ; Tickler et al., ; Yan et al., 2021).

Figure 4

Molecular resistance mechanisms in non-carbapenemase-producing carbapenem-resistant E. coli/carbapenem non-susceptible E.coli (non-CP-CREc /non-CP-CNEc) (Chia et al., ; Ma et al., ; Dupont et al., ; Ho et al., ; Dagher et al., ; Senchyna et al., ; Al-Farsi et al., ; Tian et al., 2020).