Academic Journal
Individual host variation in single-cell responses to enteroaggregative Escherichia coli infection modeled with human colon organoids.
| Τίτλος: | Individual host variation in single-cell responses to enteroaggregative Escherichia coli infection modeled with human colon organoids. |
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| Συγγραφείς: | Qiu L; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Patel TD; Pediatric Oncology, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA., Jones HE; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA., Coarfa C; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.; Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas, USA., Maresso AW; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.; TAILФR Labs, Baylor College of Medicine, Houston, Texas, USA. |
| Πηγή: | MSphere [mSphere] 2026 Sep 29; Vol. 11 (9), pp. e0075825. Date of Electronic Publication: 2026 Aug 11. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101674533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2379-5042 (Electronic) Linking ISSN: 23795042 NLM ISO Abbreviation: mSphere Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Society for Microbiology, [2015]- |
| Ιατρικοί όροι (MeSH): | Organoids*/microbiology , Colon*/microbiology , Colon*/cytology , Escherichia coli*/pathogenicity , Escherichia coli Infections*/microbiology , Host-Pathogen Interactions*, Epithelial Cells/microbiology ; Humans ; Single-Cell Analysis ; Adult ; Single-Cell Gene Expression Analysis |
| Περίληψη: | Enteroaggregative Escherichia coli (EAEC) is a leading cause of diarrhea worldwide. Interestingly, EAEC disease outcomes vary dramatically among infected individuals, ranging from asymptomatic colonization to acute and chronic diarrhea. While previous research has focused on EAEC virulence factors, emerging evidence suggests that host genetic and cellular background may be equally important in determining disease susceptibility. To understand host-driven disease heterogeneity, we performed single-cell RNA sequencing on human colon organoids (HCOs) derived from three healthy adult donors following EAEC 042 infection. Surprisingly, despite comparable EAEC adherence across donors, we observed striking donor-specific responses to infection at multiple levels. A total of seven distinct colonic epithelial cell clusters were identified, with striking donor-specific baseline compositions. Following infection, the HCO donors exhibited three distinct response phenotypes evident in both cell type remodeling and gene regulation: hyperresponsive, intermediate, and non-responsive. We further observed extensive donor-specific cell-cell communication networks at baseline and after EAEC infection. This study suggests that the heterogeneity in host epithelial response to EAEC infection extends to the single-cell level. While the colonic regions from which the HCOs were derived represent a potential confounding factor, the magnitude of organoid-to-organoid variation exceeded previously reported regional differences, suggesting intrinsic host factors as a crucial part of response heterogeneity. These findings establish a paradigm for understanding infectious disease susceptibility through the human organoid model system.IMPORTANCEUnderstanding why similar pathogen exposures produce vastly different clinical outcomes is critical for combating infectious diseases. By conducting single-cell RNA sequencing on human colon organoids derived from three different donors, we show that each donor possesses unique intrinsic cellular compositions and distinct transcriptomic responses to enteroaggregative Escherichia coli (EAEC) infection. These findings challenge the traditional pathogen-focused paradigm and highlight the critical role of host factors in infectious disease outcomes. This study also validates human organoids as a powerful platform for studying host heterogeneity, which may help predict disease susceptibility and optimize treatment for diverse patient populations in the future. |
| Competing Interests: | The authors declare no conflict of interest. |
| Σχόλια: | Update of: bioRxiv. 2025 Oct 24:2025.10.24.684350. doi: 10.1101/2025.10.24.684350.. (PMID: 41279052) |
| References: | Infect Immun. 1998 Jul;66(7):3155-63. (PMID: 9632580) Stem Cell Reports. 2021 Sep 14;16(9):2364-2378. (PMID: 34450035) PLoS Pathog. 2020 Sep 28;16(9):e1008851. (PMID: 32986782) Stem Cell Reports. 2023 Jun 13;18(6):1255-1270. (PMID: 37315519) J Med Microbiol. 2013 Dec;62(Pt 12):1828-1834. (PMID: 24008499) Signal Transduct Target Ther. 2024 Mar 22;9(1):61. (PMID: 38514615) Curr Top Microbiol Immunol. 2018;416:27-50. (PMID: 30232602) PLoS One. 2015 Jun 26;10(6):e0131506. (PMID: 26114631) Annu Rev Med. 2022 Jan 27;73:167-182. (PMID: 34644153) Nature. 2017 Nov 16;551(7680):333-339. (PMID: 29144463) Clin Microbiol Rev. 2014 Jul;27(3):614-30. (PMID: 24982324) Pediatr Infect Dis J. 1987 Sep;6(9):829-31. (PMID: 3313248) J Infect Dis. 1998 Jan;177(1):88-96. (PMID: 9419174) Infect Immun. 1999 Nov;67(11):5587-96. (PMID: 10531204) mBio. 2024 Aug 14;15(8):e0131624. (PMID: 38953637) Genes Cancer. 2023 Feb 01;14:12-29. (PMID: 36741860) RNA Biol. 2021 May;18(5):796-808. (PMID: 33406999) J Infect Dis. 1995 Feb;171(2):465-8. (PMID: 7844392) Infect Immun. 2018 Jan 22;86(2):. (PMID: 29084893) Infect Immun. 2020 Aug 19;88(9):. (PMID: 32631917) Cell Mol Gastroenterol Hepatol. 2022;13(5):1554-1589. (PMID: 35176508) Mol Cell Proteomics. 2014 Sep;13(9):2277-87. (PMID: 24889196) mBio. 2018 Feb 20;9(1):. (PMID: 29463660) J Microbiol. 2011 Feb;49(1):46-52. (PMID: 21369978) Cell. 2019 Aug 22;178(5):1231-1244.e11. (PMID: 31402172) Clin Infect Dis. 1999 Aug;29(2):335-8. (PMID: 10476738) Scand J Infect Dis. 2009;41(2):105-8. (PMID: 19107675) Nat Commun. 2021 Feb 17;12(1):1088. (PMID: 33597522) Nature. 2021 Sep;597(7875):250-255. (PMID: 34497389) Nature. 2023 Jul;619(7970):572-584. (PMID: 37468586) Stem Cells. 2014 May;32(5):1083-91. (PMID: 24496776) Front Immunol. 2021 Jul 29;12:655960. (PMID: 34394073) Infect Immun. 1996 Nov;64(11):4751-60. (PMID: 8890236) J Infect Dis. 2010 Aug 15;202(4):506-14. (PMID: 20594107) mSphere. 2025 Aug 26;10(8):e0082024. (PMID: 40772719) J Med Microbiol. 1999 Nov;48(11):1011-1016. (PMID: 10535645) EcoSal Plus. 2025 Dec 16;13(1):eesp00112024. (PMID: 40586580) Sci Rep. 2019 Mar 26;9(1):5233. (PMID: 30914743) Curr Opin Infect Dis. 2018 Oct;31(5):433-439. (PMID: 30063473) J Infect Dis. 1998 Jul;178(1):185-90. (PMID: 9652439) Sci Rep. 2020 Jun 29;10(1):10533. (PMID: 32601325) Germs. 2022 Jun 30;12(2):262-275. (PMID: 36504617) Mol Syst Biol. 2021 Jul;17(7):e9833. (PMID: 34309190) |
| Grant Information: | CARB U19 AI157981-03, BCRC U19 AI116497-08, GCID U19 AI144297-05 United States NH NIH HHS; RP210227, RP200504 Cancer Prevention and Research Institute of Texas; P30 CA125123, P42 ES027725, P30 ES030285, 1S10OD032185 United States NH NIH HHS |
| Contributed Indexing: | Keywords: Escherichia coli; bacterial infection; bioinformatics; enteric infection; epithelial cells; host heterogeneity; host susceptibility; host-pathogen interactions; human intestinal organoids; infection response; innate immunity; single-cell RNA sequencing |
| Entry Date(s): | Date Created: 20260811 Date Completed: 20260929 Latest Revision: 20261001 |
| Update Code: | 20261001 |
| PubMed Central ID: | PMC13621869 |
| DOI: | 10.1128/msphere.00758-25 |
| PMID: | 42578676 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2379-5042 |
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| DOI: | 10.1128/msphere.00758-25 |