Enterohemorrhagic Escherichia coli infection inhibits colonic thiamin pyrophosphate uptake via transcriptional mechanism


Autoři: Kasin Yadunandam Anandam aff001;  Subrata Sabui aff001;  Morgan M. Thompson aff001;  Sreya Subramanian aff001;  Hamid M. Said aff001
Působiště autorů: University of California-Irvine School of Medicine, Department of Physiology and Biophysics, Irvine, California, United States of America aff001;  Veterans Affairs Medical Center, Department of Medical Research, Long Beach, California, United States of America aff002;  University of California-Irvine School of Medicine, Department of Medicine, Irvine, California, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224234

Souhrn

Colonocytes possess a specific carrier-mediated uptake process for the microbiota-generated thiamin (vitamin B1) pyrophosphate (TPP) that involves the TPP transporter (TPPT; product of the SLC44A4 gene). Little is known about the effect of exogenous factors (including enteric pathogens) on the colonic TPP uptake process. Our aim in this study was to investigate the effect of Enterohemorrhagic Escherichia coli (EHEC) infection on colonic uptake of TPP. We used human-derived colonic epithelial NCM460 cells and mice in our investigation. The results showed that infecting NCM460 cells with live EHEC (but not with heat-killed EHEC, EHEC culture supernatant, or with non-pathogenic E. Coli) to lead to a significant inhibition in carrier-mediated TPP uptake, as well as in level of expression of the TPPT protein and mRNA. Similarly, infecting mice with EHEC led to a significant inhibition in colonic TPP uptake and in level of expression of TPPT protein and mRNA. The inhibitory effect of EHEC on TPP uptake by NCM460 was found to be associated with reduction in the rate of transcription of the SLC44A4 gene as indicated by the significant reduction in the activity of the SLC44A4 promoter transfected into EHEC infected cells. The latter was also associated with a marked reduction in the level of expression of the transcription factors CREB-1 and ELF3, which are known to drive the activity of the SLC44A4 promoter. Finally, blocking the ERK1/2 and NF-kB signaling pathways in NCM460 cells significantly reversed the level of EHEC inhibition in TPP uptake and TPPT expression. Collectively, these findings show, for the first time, that EHEC infection significantly inhibit colonic uptake of TPP, and that this effect appears to be exerted at the level of SLC44A4 transcription and involves the ERK1/2 and NF-kB signaling pathways.

Klíčová slova:

Colon – ERK signaling cascade – Escherichia coli infections – Gastrointestinal tract – Gene expression – Protein expression – Signal inhibition – Enterohaemorrhagic Escherichia coli


Zdroje

1. Berdanier CD. Advanced Nutrition: Micronutrients. Boca Raton, FL: CRC, 1998, p. 80–88.

2. Bettendorff L, Wins P. Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors. FEBS J. 2009; 276: 2917–2925. doi: 10.1111/j.1742-4658.2009.07019.x 19490098

3. Calingasan NY, Chun WJ, Park LC, Uchida K, Gibson GE. Oxidative stress is associated with region-specific neuronal death during thiamine deficiency. J Neuropathol Exp Neurol. 1999; 58: 946–958. doi: 10.1097/00005072-199909000-00005 10499437

4. Bettendorff L, Goessens G, Sluse F, Wins P, Bureau M, Laschet J, et al. Thiamine deficiency in cultured neuroblastoma cells: effect on mitochondrial function and peripheral benzodiazepine receptors. J Neurochem 1995; 64: 2013–2021. doi: 10.1046/j.1471-4159.1995.64052013.x 7722487

5. Karuppagounder SS, Shi Q, Xu H, Gibson GE. Changes in inflammatory processes associated with selective vulnerability following mild impairment of oxidative metabolism. Neurobiol Dis. 2007; 26: 353–362. doi: 10.1016/j.nbd.2007.01.011 17398105

6. Vemuganti R, Kalluri H, Yi JH, Bowen KK, Hazell AS. Gene expression changes in thalamus and inferior colliculus associated with inflammation, cellular stress, metabolism and structural damage in thiamine deficiency. Eur J Neurosci. 2006; 23: 1172–1188. doi: 10.1111/j.1460-9568.2006.04651.x 16553781

7. Tanphaichirt V. Modern Nutrition in Health and Disease. New York: Lea and Febiger, 1994, p. 359–375.

8. Victor M, Adams RD, Collins GH. The Wernicke-Korsakoff Syndrome and Related Neurological Disorders Due to Alcoholism and Malnutrition. Philadelphia, PA: Davis, 1989.

9. Saito N, Kimura M, Kuchiba A, Itokawa Y. Blood thiamine levels in outpatients with diabetes mellitus. J Nutr Sci Vitaminol. (Tokyo). 1987; 33: 421–430. doi: 10.3177/jnsv.33.421 3451944

10. Rindi G, Laforenza U. Thiamine intestinal transport and related issues: recent aspects. Proc Soc Exp Biol Med. 2000; 224: 246–255. doi: 10.1046/j.1525-1373.2000.22428.x 10964259

11. Said HM. Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011; 437: 357–372. doi: 10.1042/BJ20110326 21749321

12. Said HM. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas. Am J Physiol Gastrointest Liver Physiol. 2013; 305: G601–G610. doi: 10.1152/ajpgi.00231.2013 23989008

13. Fleming JC, Tartaglini E, Steinkamp MP, Schorderet DF, Cohen N, Neufeld EJ. The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter. Nat Genet. 1999; 22: 305–308. doi: 10.1038/10379 10391222

14. Rajgopal A, Edmondson A, Goldman ID, Zhao R. SLC19A3 encodes a second thiamine transporter ThTr2. Biochim Biophys Acta. 2001; 1537: 175–178. doi: 10.1016/s0925-4439(01)00073-4 11731220

15. Reidling JC, Lambrecht N, Kassir M, Said HM. Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice. Gastroenterol. 2010; 138: 1802–1809.

16. Said HM, Balamurugan K, Subramanian VS, Marchant JS. Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine. Am J Physiol Gastrointest Liver Physiol. 2004; 286: G491–G498. doi: 10.1152/ajpgi.00361.2003 14615284

17. Subramanya SB, Subramanian VS, Said HM. Chronic alcohol consumption and intestinal thiamin absorption: effects on physiological and molecular parameters of the uptake process. Am J Physiol Gastrointest Liver Physiol. 2010; 299: G23–G31. doi: 10.1152/ajpgi.00132.2010 20448146

18. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. MetaHIT Consortium. Enterotypes of the human gut microbiome. Nature 2011; 473: 174–180. doi: 10.1038/nature09944 21508958

19. Said HM, Ortiz A, Subramanian VS, Neufeld EJ, Moyer MP, Dudeja PK. Mechanism of thiamine uptake by human colonocytes: studies with cultured colonic epithelial cell line NCM460. Am J Physiol Gastrointest Liver Physiol. 2001; 281: G144–G150. doi: 10.1152/ajpgi.2001.281.1.G144 11408266

20. Nabokina SM, Said HM. A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2012; 303: G389–G395. doi: 10.1152/ajpgi.00151.2012 22628036

21. Nabokina SM, Inoue K, Subramanian VS, Valle JE, Yuasa H, Said HM. Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter. J Biol Chem. 2014; 289: 4405–4416. doi: 10.1074/jbc.M113.528257 24379411

22. Said HM, Seetharam B. Intestinal absorption of water-soluble vitamins. In: Physiology of the Gastrointestinal Tract (4th ed.), edited by Johnson LR. San Diego, CA: Elsevier, 2006, p. 1791–1825.

23. Nabokina SM, Ramos MB, Said HM. Mechanism(s) involved in the colon-specific expression of the thiamine pyrophosphate (TPP) transporter. PLoS One 2016; 11: e0149255. doi: 10.1371/journal.pone.0149255 26901654

24. Nabokina SM, Ramos MB, Valle JE, Said HM. Regulation of basal promoter activity of the human thiamine pyrophosphate transporter SLC44A4 in human intestinal epithelial cells. Am J Physiol Cell Physiol. 2015; 308: C750–C757. doi: 10.1152/ajpcell.00381.2014 25715703

25. Anandam KY, Srinivasan P, Subramanian VS, Said HM. Molecular mechanisms involved in the adaptive regulation of the colonic thiamin pyrophosphate uptake process. Am J Physiol Cell Physiol. 2017; 313: C655–C663. doi: 10.1152/ajpcell.00169.2017 28931541

26. Sears CL and Kaper JB. Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiol Rev. 1996; 60: 167–215. 8852900

27. Hecht G, Marrero JA, Danilkovich A, Matkowskyj KA, Savkovic SD, Koutsouris A, et al. Pathogenic Escherichia coli increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression. J Clin Invest. 1999; 104: 253–262. doi: 10.1172/JCI6373 10430606

28. Croxen MA, Finlay BB. Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbiol. 2010; 8: 26–38. doi: 10.1038/nrmicro2265 19966814

29. Battle SE, Brady MJ, Vanaja SK, Leong JM, Hecht GA. Actin pedestal formation by enterohemorrhagic Escherichia coli enhances bacterial host cell attachment and concomitant type III translocation. Infect Immun. 2014; 82: 3713–3722. doi: 10.1128/IAI.01523-13 24958711

30. Lewis SB, Cook V, Tighe R, Schüller S. Enterohemorrhagic Escherichia coli colonization of human colonic epithelium in vitro and ex vivo. Infect Immun. 2015; 83: 942–949. doi: 10.1128/IAI.02928-14 25534942

31. Ho NK, Ossa JC, Silphaduang U, Johnson R, Johnson-Henry KC, Sherman PM. Enterohemorrhagic Escherichia coli O157:H7 shiga toxins inhibit gamma interferon-mediated cellular activation. Infect Immun. 2012; 80: 2307–2315. doi: 10.1128/IAI.00255-12 22526675

32. Shimizu T, Ohta Y, Noda M. Shiga toxin 2 is specifically released from bacterial cells by two different mechanisms. Infect Immun. 2009; 77: 2813–2823. doi: 10.1128/IAI.00060-09 19380474

33. Roxas JL, Koutsouris A, Bellmeyer A, Tesfay S, Royan S, Falzari K, et al. Enterohemorrhagic E. coli alters murine intestinal epithelial tight junction protein expression and barrier function in a shiga toxin independent manner. Lab Invest. 2010; 90: 1152–1168. doi: 10.1038/labinvest.2010.91 20479715

34. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(delta delta C(T)) method. Methods 2001; 25: 402–408. doi: 10.1006/meth.2001.1262 11846609

35. Golan L, Gonen E, Yagel S, Rosenshine I, Shpigel NY. Enterohemorrhagic Escherichia coli induce attaching and effacing lesions and hemorrhagic colitis in human and bovine intestinal xenograft models. Dis Model Mech. 2011; 4: 86–94. doi: 10.1242/dmm.005777 20959635

36. Dahan S, Busuttil V, Imbert V, Peyron JF, Rampal P, Czerucka1 D. Enterohemorrhagic Escherichia coli infection induces interleukin-8 production via activation of mitogen-activated protein kinases and the transcription factors NF-κB and AP-1 in T84 cells. Infect Immun. 2002; 70: 2304–2310. doi: 10.1128/IAI.70.5.2304-2310.2002 11953364

37. Berin MC, Darfeuille-Michaud A, Egan LJ, Miyamoto Y, Kagnoff MF. Role of EHEC O157:H7 virulence factors in the activation of intestinal epithelial cell NF-κB and MAP kinase pathways and the upregulated expression of interleukin 8. Cell Microbiol. 2002; 4: 635–648. 12366401

38. Sanchez-Villamil J, Tapia-Pastrana G, and Navarro-Garcia F. Pathogenic lifestyles of E. coli pathotypes in a standardized epithelial cell model influence inflammatory signaling pathways and cytokines secretion. Front Cell Infect Microbiol. 2016; 6: 120. doi: 10.3389/fcimb.2016.00120 27774437

39. Center for Disease Control and Prevention. Ongoing multistate outbreak of Escherichia coli serotype O157:H7 infections associated with consumption of fresh spinach—United States, September 2006. Morb Mortal Wkly Rep. 2006; 55: 1045–1046.

40. Laiko M, Murtazina R, Malyukova I, Zhu C, Boedeker EC, Gutsal O, et al. Shiga toxin 1 interaction with enterocytes causes apical protein mistargeting through the depletion of intracellular galectin-3. Exp Cell Res. 2010 Feb 15;316: 657–66. doi: 10.1016/j.yexcr.2009.09.002 19744479

41. Li Z, Bell C, Buret A, Robins-Browne R, Stiel D, O'Loughlin E. The effect of enterohemorrhagic Escherichia coli O157:H7 on intestinal structure and solute transport in rabbits. Gastroenterol. 1993; 104: 467–474.

42. Elliott E, Li Z, Bell C, Stiel D, Buret A, Wallace J, et al. Modulation of host response to Escherichia coli o157:H7 infection by anti-CD18 antibody in rabbits. Gastroenterol. 1994; 106: 1554–1561.

43. Bell CJ, Elliott EJ, Wallace JL, Redmond DM, Payne J, Li Z, et al. Do eicosanoids cause colonic dysfunction in experimental E coli O157:H7 (EHEC) infection? Gut. 2000; 46: 806–812. doi: 10.1136/gut.46.6.806 10807892


Článek vyšel v časopise

PLOS One


2019 Číslo 10