Whole genome analyses of CMY-2-producing Escherichia coli isolates from humans, animals and food in Germany

Background: Resistance to 3rd-generation cephalosporins in Escherichia coli is mostly mediated by extended-spectrum beta-lactamases (ESBLs) or AmpC beta-lactamases. Besides overexpression of the species-specific chromosomal ampC gene, acquisition of plasmid-encoded ampC genes, e.g. bla(CMY-2), has been described worldwide in E coli from humans and animals. To investigate a possible transmission of bla(CMY-2) along the food production chain, we conducted a next-generation sequencing (NGS)-based analysis of 164 CMY-2-producing E coli isolates from humans, livestock animals and foodstuff from Germany. Results: The data of the 164 sequenced isolates revealed 59 different sequence types (STs); the most prevalent ones were ST38 (n = 19), ST131 (n = 16) and ST117 (n = 13). Two STs were present in all reservoirs: ST131 (human n = 8; food n = 2; animal n = 6) and ST38 (human n = 3; animal n = 9; food n = 7). All but one CMY-2-producing ST131 isolates belonged to the Glade B (fimH22) that differed substantially from the worldwide dominant CTX-M-15-producing clonal lineage ST131-O25b Glade C (fimH30). Plasmid replicon types Inch (n = 61) and IncK (n = 72) were identified for the majority of bla(CMY-2)-carrying plasmids. Plasmid sequence comparisons showed a remarkable sequence identity, especially for IncK plasmids. Associations of replicon types and distinct STs were shown for IncK and ST57, ST429 and ST38 as well as for Incl1 and ST58. Additional beta-lactamase genes (bla(TEM), bla(CTX-M), bla(OXA), bla(SHV)) were detected in 50% of the isolates, and twelve E. coli from chicken and retail chicken meat carried the colistin resistance gene mcr-1. Conclusion: We found isolates of distinct E. coli clonal lineages (ST131 and ST38) in all three reservoirs. However, a direct clonal relationship of isolates from food animals and humans was only noticeable for a few cases. The CMY-2-producing E coli-ST131 represents a clonal lineage different from the CTX-M-15-producing ST131-O25b cluster. Apart from the ST-driven spread, plasmid-mediated spread, especially via Inc1 and IncK plasmids, likely plays an important role for emergence and transmission of bla(CMY-2) between animals and humans.