Enterohemorrhagic Escherichia Coli Senses Low Biotin Status in the Large Intestine for Colonization and Infection

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Mar 21

PMID 25791315

Citations 59

Authors

Bin Yang

Lu Feng

Fang Wang

Lei Wang

Affiliations

Soon will be listed here.

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is an important foodborne pathogen that infects humans by colonizing the large intestine. Here we identify a virulence-regulating pathway in which the biotin protein ligase BirA signals to the global regulator Fur, which in turn activates LEE (locus of enterocyte effacement) genes to promote EHEC adherence in the low-biotin large intestine. LEE genes are repressed in the high-biotin small intestine, thus preventing adherence and ensuring selective colonization of the large intestine. The presence of this pathway in all nine EHEC serotypes tested indicates that it is an important evolutionary strategy for EHEC. The pathway is incomplete in closely related small-intestinal enteropathogenic E. coli due to the lack of the Fur response to BirA. Mice fed with a biotin-rich diet show significantly reduced EHEC adherence, indicating that biotin might be useful to prevent EHEC infection in humans.

Citing Articles

A novel small RNA regulates Locus of Enterocyte Effacement and site-specific colonization of enterohemorrhagic O157:H7 in gut.

Han R, Qian Y, Zheng C Front Cell Infect Microbiol. 2025; 14:1517328.

PMID: 39882344 PMC: 11774850. DOI: 10.3389/fcimb.2024.1517328.

Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria.

Li X, Pang Y, Jiang L, Liu L, Zhou J, Jin C Nat Commun. 2025; 16(1):607.

PMID: 39799152 PMC: 11724981. DOI: 10.1038/s41467-025-55982-z.

Key roles of two-component systems in intestinal signal sensing and virulence regulation in enterohemorrhagic Escherichia coli.

Sun H, Huang D, Pang Y, Chen J, Kang C, Zhao M FEMS Microbiol Rev. 2024; 48(6).

PMID: 39537200 PMC: 11644481. DOI: 10.1093/femsre/fuae028.

Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives.

Karachaliou C, Livaniou E Int J Mol Sci. 2024; 25(12).

PMID: 38928282 PMC: 11203980. DOI: 10.3390/ijms25126578.

CobB-mediated deacetylation of the chaperone CesA regulates O157:H7 virulence.

Li L, Yang B, Wang J, Wei Y, Xiang B, Liu Y Gut Microbes. 2024; 16(1):2331435.

PMID: 38502202 PMC: 10956630. DOI: 10.1080/19490976.2024.2331435.

References

Chakravartty V, Cronan J . Altered regulation of Escherichia coli biotin biosynthesis in BirA superrepressor mutant strains. J Bacteriol. 2012; 194(5):1113-26. PMC: 3294782. DOI: 10.1128/JB.06549-11. View

Bertin Y, Chaucheyras-Durand F, Robbe-Masselot C, Durand A, de la Foye A, Harel J . Carbohydrate utilization by enterohaemorrhagic Escherichia coli O157:H7 in bovine intestinal content. Environ Microbiol. 2012; 15(2):610-22. PMC: 3558604. DOI: 10.1111/1462-2920.12019. View

Barnett Foster D . Modulation of the enterohemorrhagic E. coli virulence program through the human gastrointestinal tract. Virulence. 2013; 4(4):315-23. PMC: 3710334. DOI: 10.4161/viru.24318. View

Phillips A, Frankel G . Intimin-mediated tissue specificity in enteropathogenic Escherichia coli interaction with human intestinal organ cultures. J Infect Dis. 2000; 181(4):1496-500. DOI: 10.1086/315404. View

Datsenko K, Wanner B . One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A. 2000; 97(12):6640-5. PMC: 18686. DOI: 10.1073/pnas.120163297. View

Reece S, Simmons C, Fitzhenry R, Matthews S, Phillips A, Dougan G . Site-directed mutagenesis of intimin alpha modulates intimin-mediated tissue tropism and host specificity. Mol Microbiol. 2001; 40(1):86-98. DOI: 10.1046/j.1365-2958.2001.02371.x. View

Audia J, Webb C, FOSTER J . Breaking through the acid barrier: an orchestrated response to proton stress by enteric bacteria. Int J Med Microbiol. 2001; 291(2):97-106. DOI: 10.1078/1438-4221-00106. View

Karch H . The role of virulence factors in enterohemorrhagic Escherichia coli (EHEC)--associated hemolytic-uremic syndrome. Semin Thromb Hemost. 2001; 27(3):207-13. DOI: 10.1055/s-2001-15250. View

Murphy K, Campellone K . Lambda Red-mediated recombinogenic engineering of enterohemorrhagic and enteropathogenic E. coli. BMC Mol Biol. 2003; 4:11. PMC: 317293. DOI: 10.1186/1471-2199-4-11. View

10.

Dahan S, Knutton S, Shaw R, Crepin V, Dougan G, Frankel G . Transcriptome of enterohemorrhagic Escherichia coli O157 adhering to eukaryotic plasma membranes. Infect Immun. 2004; 72(9):5452-9. PMC: 517483. DOI: 10.1128/IAI.72.9.5452-5459.2004. View

11.

Otsuka A, Abelson J . The regulatory region of the biotin operon in Escherichia coli. Nature. 1978; 276(5689):689-94. DOI: 10.1038/276689a0. View

12.

Reber H . [Microbial infections of the small and large intestine]. Ther Umsch. 1980; 37(3):168-75. View

13.

Barker D, Campbell A . Genetic and biochemical characterization of the birA gene and its product: evidence for a direct role of biotin holoenzyme synthetase in repression of the biotin operon in Escherichia coli. J Mol Biol. 1981; 146(4):469-92. DOI: 10.1016/0022-2836(81)90043-7. View

14.

Proulx F, Turgeon J, Delage G, Lafleur L, Chicoine L . Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis. J Pediatr. 1992; 121(2):299-303. DOI: 10.1016/s0022-3476(05)81209-0. View

15.

Wilson K, Shewchuk L, Brennan R, Otsuka A, Matthews B . Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Proc Natl Acad Sci U S A. 1992; 89(19):9257-61. PMC: 50105. DOI: 10.1073/pnas.89.19.9257. View

16.

Stojiljkovic I, Baumler A, Hantke K . Fur regulon in gram-negative bacteria. Identification and characterization of new iron-regulated Escherichia coli genes by a fur titration assay. J Mol Biol. 1994; 236(2):531-45. DOI: 10.1006/jmbi.1994.1163. View

17.

Bosworth B, Samuel J, Moon H, OBrien A, Gordon V, Whipp S . Vaccination with genetically modified Shiga-like toxin IIe prevents edema disease in swine. Infect Immun. 1996; 64(1):55-60. PMC: 173727. DOI: 10.1128/iai.64.1.55-60.1996. View

18.

Kenny B, Abe A, Stein M, Finlay B . Enteropathogenic Escherichia coli protein secretion is induced in response to conditions similar to those in the gastrointestinal tract. Infect Immun. 1997; 65(7):2606-12. PMC: 175369. DOI: 10.1128/iai.65.7.2606-2612.1997. View

19.

Nataro J, Kaper J . Diarrheagenic Escherichia coli. Clin Microbiol Rev. 1998; 11(1):142-201. PMC: 121379. DOI: 10.1128/CMR.11.1.142. View

20.

Adu-Bobie J, Frankel G, Bain C, Goncalves A, Trabulsi L, Douce G . Detection of intimins alpha, beta, gamma, and delta, four intimin derivatives expressed by attaching and effacing microbial pathogens. J Clin Microbiol. 1998; 36(3):662-8. PMC: 104605. DOI: 10.1128/JCM.36.3.662-668.1998. View