Recent O-antigen diversification masks highly pathogenic STEC O104:H4

Background Shiga toxin-producing E. coli (STEC) can give rise to a range of clinical outcomes from diarrhea to the life-threatening systemic condition, hemolytic uremic syndrome (HUS). A major outbreak of HUS occurred in 2011, and was caused by a rare serotype, STEC O104:H4. Prior to 2011 and since the outbreak, STEC O104:H4 were rarely associated with human infections. Methods From 2012 to 2020 intensified STEC surveillance was performed in Germany where subtyping of ~8,000 clinical isolates by molecular methods including whole genome sequencing was carried out. Virulence traits and phylogenetic context were investigated for a subset of strains. Results A rare STEC serotype O181:H4 associated with HUS was identified, belonging to sequence type (ST) 678, like the STEC O104:H4 outbreak strain. Virulence and genomic comparisons revealed that the two strains are phylogenetically related and differ principally in the gene cluster encoding their respective lipopolysaccharide O-antigens. In addition, five other serotypes belonging to ST678 from human clinical infection were identified from diverse locations worldwide. Conclusion Our data suggest the high virulence ensemble of STEC O104:H4 remains a global threat, but that horizontal exchange of O-antigen gene clusters has cloaked the pathogen with new O-antigens, confounding interpretation of their potential risk. ### Competing Interest Statement The authors have declared no competing interest.