Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia Dranenko, NO Tutukina, MN Gelfand, MS Kondrashov, Fyodor ; https://orcid.org/0000-0001-8243-4694 Bochkareva, Olga ; https://orcid.org/0000-0003-1006-6639 ddc:570 Until recently, Shigella and enteroinvasive Escherichia coli were thought to be primate-restricted pathogens. The base of their pathogenicity is the type 3 secretion system (T3SS) encoded by the pINV virulence plasmid, which facilitates host cell invasion and subsequent proliferation. A large family of T3SS effectors, E3 ubiquitin-ligases encoded by the ipaH genes, have a key role in the Shigella pathogenicity through the modulation of cellular ubiquitination that degrades host proteins. However, recent genomic studies identified ipaH genes in the genomes of Escherichia marmotae, a potential marmot pathogen, and an E. coli extracted from fecal samples of bovine calves, suggesting that non-human hosts may also be infected by these strains, potentially pathogenic to humans. We performed a comparative genomic study of the functional repertoires in the ipaH gene family in Shigella and enteroinvasive Escherichia from human and predicted non-human hosts. We found that fewer than half of Shigella genomes had a complete set of ipaH genes, with frequent gene losses and duplications that were not consistent with the species tree and nomenclature. Non-human host IpaH proteins had a diverse set of substrate-binding domains and, in contrast to the Shigella proteins, two variants of the NEL C-terminal domain. Inconsistencies between strains phylogeny and composition of effectors indicate horizontal gene transfer between E. coli adapted to different hosts. These results provide a framework for understanding of ipaH-mediated host-pathogens interactions and suggest a need for a genomic study of fecal samples from diseased animals. Springer Nature 2022 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/11344 https://research-explorer.ista.ac.at/download/11344/11349 Dranenko N, Tutukina M, Gelfand M, Kondrashov F, Bochkareva O. Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia. <i>Scientific Reports</i>. 2022;12. doi:<a href="https://doi.org/10.1038/s41598-022-10827-3">10.1038/s41598-022-10827-3</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-022-10827-3 info:eu-repo/semantics/altIdentifier/issn/2045-2322 info:eu-repo/semantics/altIdentifier/wos/000788639400032 info:eu-repo/semantics/altIdentifier/pmid/35477739 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess