Genome-wide association study of hemolytic uremic syndrome causing Shiga toxin-producing Escherichia coli from Sweden, 1994-2018.
| Title: | Genome-wide association study of hemolytic uremic syndrome causing Shiga toxin-producing Escherichia coli from Sweden, 1994-2018. |
|---|---|
| Authors: | Matussek A; Department of Microbiology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.; Department of Microbiology, Division of Laboratory Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.; Laboratory Medicine, Department of Clinical and Experimental Medicine, Jönköping Region County, Linköping University, Jönköping, Sweden.; Mernelius S; Laboratory Medicine, Department of Clinical and Experimental Medicine, Jönköping Region County, Linköping University, Jönköping, Sweden.; Department of Laboratory Medicine, Jönköping, Sweden.; Chromek M; Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.; Zhang J; Fonterra Research and Development Centre, Dairy Farm Road, Palmerston North, New Zealand.; Frykman A; Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.; Hansson S; Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.; Georgieva V; Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.; Xiong Y; State Key Laboratory of Infectious Disease Prevention and Control, Chinese Center for Disease Control and Prevention, National Institute for Communicable Disease Control and Prevention, Beijing, China.; Bai X; Department of Microbiology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway. xiangning.bai@ki.se.; Department of Microbiology, Division of Laboratory Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. xiangning.bai@ki.se.; Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden. xiangning.bai@ki.se. |
| Source: | European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology [Eur J Clin Microbiol Infect Dis] 2023 Jun; Vol. 42 (6), pp. 771-779. Date of Electronic Publication: 2023 Apr 27. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer Country of Publication: Germany NLM ID: 8804297 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-4373 (Electronic) Linking ISSN: 09349723 NLM ISO Abbreviation: Eur J Clin Microbiol Infect Dis Subsets: MEDLINE |
| Imprint Name(s): | Publication: Berlin : Springer; Original Publication: [Wiesbaden, Federal Republic of Germany] : Vieweg, [c1988- |
| MeSH Terms: | Escherichia coli Proteins*/genetics ; Escherichia coli Infections*/complications ; Escherichia coli Infections*/epidemiology ; Escherichia coli Infections*/microbiology ; Hemolytic-Uremic Syndrome*/epidemiology ; Hemolytic-Uremic Syndrome*/microbiology ; Shiga-Toxigenic Escherichia coli*; Sweden/epidemiology ; Humans ; Genome-Wide Association Study ; Phylogeny |
| Abstract: | Shiga toxin-producing Escherichia coli (STEC) infection can cause clinical manifestations ranging from diarrhea to potentially fatal hemolytic uremic syndrome (HUS). This study is aimed at identifying STEC genetic factors associated with the development of HUS in Sweden. A total of 238 STEC genomes from STEC-infected patients with and without HUS between 1994 and 2018 in Sweden were included in this study. Serotypes, Shiga toxin gene (stx) subtypes, and virulence genes were characterized in correlation to clinical symptoms (HUS and non-HUS), and pan-genome wide association study was performed. Sixty-five strains belonged to O157:H7, and 173 belonged to non-O157 serotypes. Our study revealed that strains of O157:H7 serotype especially clade 8 were most commonly found in patients with HUS in Sweden. stx2a and stx2a + stx2c subtypes were significantly associated with HUS. Other virulence factors associated with HUS mainly included intimin (eae) and its receptor (tir), adhesion factors, toxins, and secretion system proteins. Pangenome wide-association study identified numbers of accessory genes significantly overrepresented in HUS-STEC strains, including genes encoding outer membrane proteins, transcriptional regulators, phage-related proteins, and numerous genes related to hypothetical proteins. Whole-genome phylogeny and multiple correspondence analysis of pangenomes could not differentiate HUS-STEC from non-HUS-STEC strains. In O157:H7 cluster, strains from HUS patients clustered closely; however, no significant difference in virulence genes was found in O157 strains from patients with and without HUS. These results suggest that STEC strains from different phylogenetic backgrounds may independently acquire genes determining their pathogenicity and confirm that other non-bacterial factors and/or bacteria-host interaction may affect STEC pathogenesis.; (© 2023. The Author(s).) |
| References: | Infect Immun. 2011 Mar;79(3):1329-37. (PMID: 21199911); PLoS One. 2014 Oct 31;9(10):e111788. (PMID: 25360710); Open Forum Infect Dis. 2014 Aug 12;1(2):ofu061. (PMID: 25734131); J Appl Microbiol. 2011 Jan;110(1):323-32. (PMID: 21073642); Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4868-73. (PMID: 18332430); Genome Biol. 2016 Nov 25;17(1):238. (PMID: 27887642); Compr Rev Food Sci Food Saf. 2022 May;21(3):2363-2390. (PMID: 35306744); Trop Med Infect Dis. 2022 Nov 07;7(11):. (PMID: 36355898); Int J Med Microbiol. 2016 Feb;306(2):123-30. (PMID: 26935026); Clin Lab Med. 2015 Jun;35(2):247-72. (PMID: 26004641); Bioinformatics. 2014 Jul 15;30(14):2068-9. (PMID: 24642063); PLoS One. 2010 Apr 21;5(4):e10167. (PMID: 20422047); Bioinformatics. 2015 Nov 15;31(22):3691-3. (PMID: 26198102); Med Mal Infect. 2018 May;48(3):167-174. (PMID: 29054297); Appl Environ Microbiol. 2004 Jan;70(1):61-8. (PMID: 14711626); BMC Infect Dis. 2015 Aug 11;15:324. (PMID: 26259588); Bioinformatics. 2018 Sep 1;34(17):3025-3027. (PMID: 29608746); Microbiol Spectr. 2022 Aug 31;10(4):e0066022. (PMID: 35730965); Microbiol Spectr. 2014 Aug;2(4):EHEC-0024-2013. (PMID: 25530917); Curr Biol. 2019 Oct 21;29(20):R1094-R1103. (PMID: 31639358); J Med Microbiol. 2021 Jul;70(7):. (PMID: 34309502); J Clin Microbiol. 2012 Sep;50(9):2951-63. (PMID: 22760050); Lancet. 2005 Mar 19-25;365(9464):1073-86. (PMID: 15781103); Emerg Infect Dis. 2004 May;10(5):842-7. (PMID: 15200817); Pediatr Nephrol. 2020 Sep;35(9):1749-1759. (PMID: 32323005); Virulence. 2021 Dec;12(1):1296-1305. (PMID: 33939581); Toxins (Basel). 2020 Jan 21;12(2):. (PMID: 31973203); Pediatr Nephrol. 2021 Sep;36(9):2811-2817. (PMID: 33604727); Microorganisms. 2018 Apr 27;6(2):. (PMID: 29702577); Nucleic Acids Res. 2015 Feb 18;43(3):e15. (PMID: 25414349); Front Microbiol. 2021 Feb 05;12:627861. (PMID: 33613494) |
| Grant Information: | SLS884041 Scandinavian Society for Antimicrobial Chemotherapy Foundation; Dnr: 2022-00277 Ruth och Richard Julins Stiftelse |
| Contributed Indexing: | Keywords: Genome-wide association study; Hemolytic uremic syndrome; Pathogenicity; Shiga toxin-producing Escherichia coli; Whole genome sequencing |
| Substance Nomenclature: | 0 (Escherichia coli Proteins) |
| Entry Date(s): | Date Created: 20230427 Date Completed: 20230512 Latest Revision: 20230513 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10172287 |
| DOI: | 10.1007/s10096-023-04600-1 |
| PMID: | 37103716 |
| Database: | MEDLINE |
Journal Article