Cited by 16Escherichia coli research studiesUrinary Tract Infections ManagementBacterial Genetics and Biotechnology

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Iron Acquisition of Urinary Tract Infection Escherichia coli Involves Pathogenicity in Caenorhabditis elegans

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Abstract

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

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Crossref · 10.3390/microorganisms9020310

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Figure 1 The number of virulence factors in clinically isolated E. coli. The boxplot indicates the number of VFs in fecal and UTI-associated isolates. The numbers of VFs between fecal and UTI-associated isolates (average 8.1 and 13.2, respectively) show a significant difference by the Mann-Whitney U test (***, p < 0.001).
Figure 1 The number of virulence factors in clinically isolated E. coli. The boxplot indicates the number of VFs in fecal and UTI-associated isolates. The numbers of VFs between fecal and UTI-associated isolates (average 8.1 and 13.2, respectively) show a significant difference by the Mann-Whitney U test (***, p < 0.001).CC BY · PubMed Central
Figure 2 Pathogenicity of E. coli clinical isolates in liquid killing assay with C. elegans. The pathogenicity (relative OD592nm value in the liquid assay) of the fecal and UTI-associated isolates were plotted. The value for MG1655 as a model strain for fecal isolate was 1.17, and that for UTI89 as a model strain for UTI associated isolate was 1.75. The horizontal bars represented the mean values. The results were analyzed statically by the Mann-Whitney U test. (***, p < 0.01). The pathogenicity of UTI-associated isolates was significantly higher than that of fecal isolates.
Figure 2 Pathogenicity of E. coli clinical isolates in liquid killing assay with C. elegans. The pathogenicity (relative OD592nm value in the liquid assay) of the fecal and UTI-associated isolates were plotted. The value for MG1655 as a model strain for fecal isolate was 1.17, and that for UTI89 as a model strain for UTI associated isolate was 1.75. The horizontal bars represented the mean values. The results were analyzed statically by the Mann-Whitney U test. (***, p < 0.01). The pathogenicity of UTI-associated isolates was significantly higher than that of fecal isolates.CC BY · PubMed Central
Figure 3 UPEC mutants defective in iron acquisition decreased the pathogenicity in C. elegans. The survivability of C. elegans (n > 100) feeding on the wild type and mutants of E. coli UTI89 defective in iron acquisition, which shows association with pathogenicity in the liquid pathogenicity assay. The results were analyzed statically by the Mantel-Cox log-rank test (*, p > 0.05; **, p > 0.01; ***, p > 0.001; ns, not significant).
Figure 3 UPEC mutants defective in iron acquisition decreased the pathogenicity in C. elegans. The survivability of C. elegans (n > 100) feeding on the wild type and mutants of E. coli UTI89 defective in iron acquisition, which shows association with pathogenicity in the liquid pathogenicity assay. The results were analyzed statically by the Mantel-Cox log-rank test (*, p > 0.05; **, p > 0.01; ***, p > 0.001; ns, not significant).CC BY · PubMed Central

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Research works printed but not linked: 38

  1. Foxman, 2002, Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs, Am. J. Med., 113, 5, 10.1016/S0002-9343(02)01054-9 · DOI
  2. Francois, 2016, The economic burden of urinary tract infections in women visiting general practices in France: A cross-sectional survey, BMC Health Serv. Res., 16, 1, 10.1186/s12913-016-1620-2 · DOI
  3. Iv, 2017, Bacterial virulence phenotypes of Escherichia coli and host susceptibility determine risk for urinary tract infections, Sci. Transl. Med., 9, eaaf1283, 10.1126/scitranslmed.aaf1283 · DOI
  4. Tan, 1999, Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis, Proc. Natl. Acad. Sci. USA, 96, 715, 10.1073/pnas.96.2.715 · DOI
  5. Garsin, 2001, A simple model host for identifying Gram-positive virulence factors, Proc. Natl. Acad. Sci. USA, 98, 10892, 10.1073/pnas.191378698 · DOI
  6. Kurz, 2003, Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening, EMBO J., 22, 1451, 10.1093/emboj/cdg159 · DOI
  7. Chou, 2013, Enterohaemorrhagic Escherichia coli O157:H7 Shiga-like toxin 1 is required for full pathogenicity and activation of the p38 mitogen-activated protein kinase pathway in Caenorhabditis elegans, Cell. Microbiol., 15, 82, 10.1111/cmi.12030 · DOI
  8. Couillault, 2002, Diverse Bacteria Are Pathogens of Caenorhabditis elegans, Infect. Immun., 70, 4705, 10.1128/IAI.70.8.4705-4707.2002 · DOI
  9. Diard, 2007, Caenorhabditis elegans as a simple model to study phenotypic and genetic virulence determinants of extraintestinal pathogenic Escherichia coli, Microbes Infect., 9, 214, 10.1016/j.micinf.2006.11.009 · DOI
  10. Kuo, 2018, A multi-omic analysis reveals the role of fumarate in regulating the virulence of enterohemorrhagic Escherichia coli, Cell Death Dis., 9, 1, 10.1038/s41419-018-0423-2 · DOI
  11. Lavigne, 2006, Virulence genotype and nematode-killing properties of extra-intestinal Escherichia coli producing CTX-M β-lactamases, Clin. Microbiol. Infect., 12, 1199, 10.1111/j.1469-0691.2006.01536.x · DOI
  12. Lavigne, J.-P., Vergunst, A.C., Goret, L., Sotto, A., Combescure, C., Blanco, J., O’Callaghan, D., and Nicolas-Chanoine, M.-H. (2012). Virulence Potential and Genomic Mapping of the Worldwide Clone Escherichia coli ST131. PLoS ONE, 7. · DOI
  13. Coors, 2013, Evaluating the Pathogenic Potential of Environmental Escherichia coli by Using the Caenorhabditis elegans Infection Model, Appl. Environ. Microbiol., 79, 2435, 10.1128/AEM.03501-12 · DOI
  14. Mao, 2012, Identification of Escherichia coli Genes Associated with Urinary Tract Infections, J. Clin. Microbiol., 50, 449, 10.1128/JCM.00640-11 · DOI
  15. Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press.
  16. Brenner, 1974, The Genetics of Caenorhabditis Elegans, Genetics, 77, 71, 10.1093/genetics/77.1.71 · DOI
  17. Clermont, 2000, Rapid and Simple Determination of the Escherichia coli Phylogenetic Group, Appl. Environ. Microbiol., 66, 4555, 10.1128/AEM.66.10.4555-4558.2000 · DOI
  18. Johnson, 2000, Extended Virulence Genotypes of Escherichia coli Strains from Patients with Urosepsis in Relation to Phylogeny and Host Compromise, J. Infect. Dis., 181, 261, 10.1086/315217 · DOI · Paper page
  19. Johnson, 2001, Clonal relationships and extended virulence genotypes among Escherichia coli isolates from women with a first or recurrent episode of cystitis, J. Infect. Dis., 183, 1508, 10.1086/320198 · DOI
  20. Johnson, J.R., Porter, S., Johnston, B., Kuskowski, M.A., Spurbeck, R.R., Mobley, H.L., and Williamson, D.A. (2015). Host characteristics and bacterial traits predict experimental virulence for Escherichia coli bloodstream isolates from patients with urosepsis. Open Forum Infectious Diseases, Oxford University Press. · DOI
  21. Luo, 2012, Similarity and Divergence of Phylogenies, Antimicrobial Susceptibilities, and Virulence Factor Profiles of Escherichia coli Isolates Causing Recurrent Urinary Tract Infections That Persist or Result from Reinfection, J. Clin. Microbiol., 50, 4002, 10.1128/JCM.02086-12 · DOI
  22. Datsenko, 2000, One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products, Proc. Natl. Acad. Sci. USA, 97, 6640, 10.1073/pnas.120163297 · DOI
  23. Baba, 2006, Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: The Keio collection, Mol. Syst. Biol., 2, 8, 10.1038/msb4100050 · DOI · Paper page
  24. Bingen, 1998, Phylogenetic analysis of Escherichia coli strains causing neonatal meningitis suggests horizontal gene transfer from a predominant pool of highly virulent B2 group strains, J. Infect. Dis., 177, 642, 10.1086/514217 · DOI
  25. Henderson, J.P., Crowley, J.R., Pinkner, J.S., Walker, J.N., Tsukayama, P., Stamm, W.E., Hooton, T.M., and Hultgren, S.J. (2009). Quantitative Metabolomics Reveals an Epigenetic Blueprint for Iron Acquisition in Uropathogenic Escherichia coli. PLoS Pathog., 5. · DOI
  26. Torres, 1997, Haem iron-transport system in enterohaemorrhagic Escherichia coli O157:H7, Mol. Microbiol., 23, 825, 10.1046/j.1365-2958.1997.2641628.x · DOI
  27. Hagan, 2009, Haem acquisition is facilitated by a novel receptor Hma and required by uropathogenic Escherichia colifor kidney infection, Mol. Microbiol., 71, 79, 10.1111/j.1365-2958.2008.06509.x · DOI
  28. Brumbaugh, 2015, Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target to Prevent Urinary Tract Infection, Infect. Immun., 83, 1443, 10.1128/IAI.02904-14 · DOI
  29. Walker, 2015, Urinary tract infections: Epidemiology, mechanisms of infection and treatment options, Nat. Rev. Genet., 13, 269, 10.1038/nrmicro3432 · DOI
  30. Watts, 2012, Contribution of Siderophore Systems to Growth and Urinary Tract Colonization of Asymptomatic Bacteriuria Escherichia coli, Infect. Immun., 80, 333, 10.1128/IAI.05594-11 · DOI
  31. Hantke, 2003, Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN, Proc. Natl. Acad. Sci. USA, 100, 3677, 10.1073/pnas.0737682100 · DOI · Paper page
  32. Anderson, 2014, Mechanisms of iron metabolism in Caenorhabditis elegans, Front. Pharmacol., 5, 113, 10.3389/fphar.2014.00113 · DOI
  33. Kortman, 2015, Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food-borne bacterial pathogens, Eur. J. Immunol., 45, 2553, 10.1002/eji.201545642 · DOI · Paper page
  34. Bandyopadhyay, 2009, Functional assessment of Nramp-like metal transporters and manganese in Caenorhabditis elegans, Biochem. Biophys. Res. Commun., 390, 136, 10.1016/j.bbrc.2009.09.082 · DOI
  35. Simonsen, 2011, Quantitative proteomics identifies ferritin in the innate immune response of C. elegans, Virulence, 2, 120, 10.4161/viru.2.2.15270 · DOI
  36. Rao, 2005, Lack of heme synthesis in a free-living eukaryote, Proc. Natl. Acad. Sci. USA, 102, 4270, 10.1073/pnas.0500877102 · DOI
  37. Flo, 2004, Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron, Nat. Cell Biol., 432, 917
  38. Robinson, 2018, The iron hand of uropathogenic Escherichia coli: The role of transition metal control in virulence, Future Microbiol., 13, 745, 10.2217/fmb-2017-0295 · DOI

Metadata

Authors
Hashimoto, M., Ma, Y.-F., Wang, S.-T., Chen, C.-S., & Teng, C.-H.
Affiliations
National Cheng Kung University (TW)
Corresponding author
  • Hashimoto, Masayuki
  • Teng, Ching-Hao
Venue
Microorganisms
Publisher
MDPI AG
Published
2021-02-02
Volume
9
Issue
2
Pages
310
ISSN
2076-2607 (ISSN-L)
OpenAlex
W3128597431
Cited by
16
References
3
Citations by year
2026: 3 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 3
FWCI
1.40
Type
journal article
Language
en
Open access
Locations
  • Microorganisms (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministry of Science and Technology, Taiwan (MOST 106-2320-B-006-033, MOST 106-2320-B-006-032, MOST 108-2319-B-002-004)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Health Sciences › Medicine › Urology › Urinary Tract Infections Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
uropathogenic Escherichia coli, urinary tract infection, iron acquisition, Caenorhabditis elegans, pathogenicity test, virulence factors, chuA, fyuA, IRP2, high-throughput screening

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CoChat. (2026). Citation check: Iron Acquisition of Urinary Tract Infection Escherichia coli Involves Pathogenicity in Caenorhabditis elegans. https://app.cochat.ai/papers/10.3390/microorganisms9020310
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Hashimoto, M., Ma, Y.-F., Wang, S.-T., Chen, C.-S., & Teng, C.-H. (2021). Iron Acquisition of Urinary Tract Infection Escherichia coli Involves Pathogenicity in Caenorhabditis elegans. Microorganisms. https://doi.org/10.3390/microorganisms9020310