article published yes NO Dranenko author MN Tutukina author MS Gelfand author Fyodor Kondrashov author 44FDEF62-F248-11E8-B48F-1D18A9856A870000-0001-8243-4694 Olga Bochkareva author C4558D3C-6102-11E9-A62E-F418E66974250000-0003-1006-6639 FyKo department ISTplus - Postdoctoral Fellowships project Evolutionary analysis of gene regulation project 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. https://research-explorer.ista.ac.at/download/11344/11349/2022_ScientificReports_Dranenko.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Springer Nature2022 eng 2045-2322 35477739 00078863940003210.1038/s41598-022-10827-3 12 Dranenko, NO, MN Tutukina, MS Gelfand, Fyodor Kondrashov, and Olga Bochkareva. “Chromosome-Encoded IpaH Ubiquitin Ligases Indicate Non-Human Enteroinvasive Escherichia.” <i>Scientific Reports</i>. Springer Nature, 2022. <a href="https://doi.org/10.1038/s41598-022-10827-3">https://doi.org/10.1038/s41598-022-10827-3</a>. Dranenko, N., Tutukina, M., Gelfand, M., Kondrashov, F., &#38; Bochkareva, O. (2022). Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia. <i>Scientific Reports</i>. Springer Nature. <a href="https://doi.org/10.1038/s41598-022-10827-3">https://doi.org/10.1038/s41598-022-10827-3</a> 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> Dranenko, NO, et al. “Chromosome-Encoded IpaH Ubiquitin Ligases Indicate Non-Human Enteroinvasive Escherichia.” <i>Scientific Reports</i>, vol. 12, 6868, Springer Nature, 2022, doi:<a href="https://doi.org/10.1038/s41598-022-10827-3">10.1038/s41598-022-10827-3</a>. N. Dranenko, M. Tutukina, M. Gelfand, F. Kondrashov, O. Bochkareva, Scientific Reports 12 (2022). N. Dranenko, M. Tutukina, M. Gelfand, F. Kondrashov, and O. Bochkareva, “Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia,” <i>Scientific Reports</i>, vol. 12. Springer Nature, 2022. Dranenko N, Tutukina M, Gelfand M, Kondrashov F, Bochkareva O. 2022. Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive Escherichia. Scientific Reports. 12, 6868. 113442022-05-02T07:08:42Z2026-04-15T08:51:09Z