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The Molecular Basis for Control of ETEC Enterotoxin Expression in Response to Environment and Host


Diarrheagenic illness remains a major disease burden in the developing world. Enterotoxigenic Escherichia coli (ETEC) are the leading bacterial cause of such disease; hundreds of millions of cases occur every year. The severe watery diarrhoea associated with ETEC infections results from the action of enterotoxins. The toxins target human gut epithelial cells and trigger the loss of water and electrolytes into the gut lumen. Oral rehydration therapy can counteract this process. Hence, glucose and salt solutions promote rehydration of the patient. In this work we show that the gene regulatory mechanisms controlling toxin expression respond directly to sugar and salt. Furthermore, we describe a molecular mechanism to explain these effects. Hence, we provide a starting point for the optimisation of oral rehydration solutions to reduce toxin expression over the course of an ETEC infection.


Vyšlo v časopise: The Molecular Basis for Control of ETEC Enterotoxin Expression in Response to Environment and Host. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004605
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004605

Souhrn

Diarrheagenic illness remains a major disease burden in the developing world. Enterotoxigenic Escherichia coli (ETEC) are the leading bacterial cause of such disease; hundreds of millions of cases occur every year. The severe watery diarrhoea associated with ETEC infections results from the action of enterotoxins. The toxins target human gut epithelial cells and trigger the loss of water and electrolytes into the gut lumen. Oral rehydration therapy can counteract this process. Hence, glucose and salt solutions promote rehydration of the patient. In this work we show that the gene regulatory mechanisms controlling toxin expression respond directly to sugar and salt. Furthermore, we describe a molecular mechanism to explain these effects. Hence, we provide a starting point for the optimisation of oral rehydration solutions to reduce toxin expression over the course of an ETEC infection.


Zdroje

1. CrossmanLC, ChaudhuriRR, BeatsonSA, WellsTJ, DesvauxM, et al. (2010) A commensal gone bad: complete genome sequence of the prototypical enterotoxigenic Escherichia coli strain H10407. J Bacteriol 192: 5822–5831.

2. SackRB (2011) The discovery of cholera - like enterotoxins produced by Escherichia coli causing secretory diarrhoea in humans. Indian J Med Res 133: 171–80.

3. GuptaSK, KeckJ, RamPK, CrumpJA, MillerMA, et al. (2008) Analysis of Data Gaps Pertaining to Enterotoxigenic Escherichia coli Infections in Low and Medium Human Development Index Countries, 1984–2005. Epidemiology and Infection 136: 721–738.

4. de HaanL, HirstTR (2004) Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms. Mol Membr Biol 21: 77–92.

5. ZhangRG, ScottDL, WestbrookML, NanceS, SpanglerBD, et al. (1995) The three-dimensional crystal structure of cholera toxin. J Mol Biol 251: 563–73.

6. TaxtA, AaslandR, SommerfeltH, NataroJ, PuntervollP (2010) Heat-stable enterotoxin of enterotoxigenic Escherichia coli as a vaccine target. Infect Immun 78: 1824–31.

7. YamamotoT, TamuraT, YokotaT (1984) Primary structure of heat-labile enterotoxin produced by Escherichia coli pathogenic for humans. J Biol Chem 259: 5037–44.

8. de HaanL, VerweijWR, FeilIK, HoltropM, HolWG, et al. (1998) Role of GM1 binding in the mucosal immunogenicity and adjuvant activity of the Escherichia coli heat-labile enterotoxin and its B subunit. Immunology 94: 424–430.

9. SaslowskyDE, te WelscherYM, ChinnapenDJ, WagnerJS, WanJ, et al. (2013) Ganglioside GM1-mediated transcytosis of cholera toxin bypasses the retrograde pathway and depends on the structure of the ceramide domain. J Biol Chem 288: 25804–9.

10. NalinDR, CashRA, IslamR, MollaM, PhillipsRA (1968) Oral maintenance therapy for cholera in adults. Lancet 2: 370–3.

11. GuerrantRL, Carneiro-FilhoBA, DillinghamRA (2003) Cholera, diarrhea, and oral rehydration therapy: triumph and indictment. Clin Infect Dis 37: 398–405.

12. BusbyS, EbrightRH (1999) Transcription activation by catabolite activator protein (CAP). J Mol Biol 293: 199–213.

13. ParkinsonG, WilsonC, GunasekeraA, EbrightYW, EbrightRH, et al. (1996) Structure of the CAP-DNA complex at 2.5 angstroms resolution: a complete picture of the protein-DNA interface. J Mol Biol 260: 395–408.

14. ZhengD, ConstantinidouC, HobmanJL, MinchinSD (2004) Identification of the CRP regulon using in vitro and in vivo transcriptional profiling. Nucleic Acids Res 32: 5874–93.

15. GraingerDC, HurdD, HarrisonM, HoldstockJ, BusbySJ (2005) Studies of the distribution of Escherichia coli cAMP-receptor protein and RNA polymerase along the E. coli chromosome. Proc Natl Acad Sci U S A 102: 17693–8.

16. RossiterAE, BrowningDF, LeytonDL, JohnsonMD, GodfreyRE, et al. (2011) Transcription of the plasmid-encoded toxin gene from enteroaggregative Escherichia coli is regulated by a novel co-activation mechanism involving CRP and Fis. Mol Microbiol 81: 179–91.

17. NavarreWW, PorwollikS, WangY, McClellandM, RosenH, et al. (2006) Selective silencing of foreign DNA with low GC content by the H-NS protein in Salmonella. Science 313: 236–8.

18. LiuY, ChenH, KenneyLJ, YanJ (2010) A divalent switch drives H-NS/DNA-binding conformations between stiffening and bridging modes. Genes Dev 24: 339–44.

19. LimCJ, LeeSY, KenneyLJ, YanJ (2012) Nucleoprotein filament formation is the structural basis for bacterial protein H-NS gene silencing. Sci Rep 2: 509.

20. MyersKS, YanH, OngIM, ChungD, LiangK, et al. (2013) Genome-scale analysis of Escherichia coli FNR reveals complex features of transcription factor binding. PLoS Genet 9 (6) e1003565.

21. DameRT, WymanC, WurmR, WagnerR, GoosenN (2002) Structural basis for H-NS-mediated trapping of RNA polymerase in the open initiation complex at the rrnB P1. J Biol Chem 277: 2146–50.

22. DormanCJ (2007) H-NS, the genome sentinel. Nat Rev Microbiol 5: 157–61.

23. AtlungT, IngmerH (1997) H-NS: a modulator of environmentally regulated gene expression. Mol Microbiol 24: 7–17.

24. SteinslandH1, Valentiner-BranthP, PerchM, DiasF, FischerTK, AabyP, MølbakK, SommerfeltH (2002) Enterotoxigenic Escherichia coli infections and diarrhea in a cohort of young children in Guinea-Bissau. J Infect Dis 186: 1740–7.

25. SinghSS, SinghN, BonocoraRP, FitzgeraldDM, WadeJT, et al. (2014) Widespread suppression of intragenic transcription initiation by H-NS. Genes Dev 28: 214–219.

26. YangJ, TauschekM, StrugnellR, Robins-BrowneRM (2005) The H-NS protein represses transcription of the eltAB operon, which encodes heat-labile enterotoxin in enterotoxigenic Escherichia coli, by binding to regions downstream of the promoter. Microbiology 151: 1199–1208.

27. BoderoMD, MunsonGP (2009) Cyclic AMP receptor protein-dependent repression of heat-labile enterotoxin. Infect Immun 77: 791–8.

28. SahlJW, RaskoDA (2012) Analysis of global transcriptional profiles of enterotoxigenic Escherichia coli isolate E24377A. Infect Immun 80: 1232–1242.

29. KansalR, RaskoDA, SahlJW, MunsonGP, RoyK (2013) Transcriptional modulation of enterotoxigenic Escherichia coli virulence genes in response to epithelial cell interactions. Infect Immun 81: 259–70.

30. ByrdW, MogSR, CasselsFJ (2003) Pathogenicity and immune response measured in mice following intranasal challenge with enterotoxigenic Escherichia coli strains H10407 and B7A. Infect Immun 71: 13–21.

31. ByrdW, BoedekerEC (2013) Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation. Vet Immunol Immunopathol 152: 57–67.

32. GuptaS, ChowdhuryR (1997) Bile affects production of virulence factors and motility of Vibrio cholerae. Infect Immun 65: 1131–1134.

33. StringerAM, SinghN, YermakovaA, PetroneBL, AmarasingheJJ, et al. (2012) FRUIT, a scar-free system for targeted chromosomal mutagenesis, epitope tagging, and promoter replacement in Escherichia coli and Salmonella enterica. PLoS One 7: e44841.

34. PageL, GriffithsL, ColeJA (1990) Different physiological roles of two independent pathways for nitrite reduction to ammonia by enteric bacteria. Arch Microbiol 154: 349–54.

35. BusbyS, KotlarzD, BucH (1983) Deletion mutagenesis of the Escherichia coli galactose operon promoter region. J Mol Biol 167: 259–274.

36. LodgeJ, FearJ, BusbyS, GunasekaranP, KaminiNR (1992) Broad host range plasmids carrying the Escherichia coli lactose and galactose operons. FEMS Microbiol Lett 74: 271–6.

37. KolbA, KotlarzD, KusanoS, IshihamaA (1995) Selectivity of the Escherichia coli RNA polymerase E sigma 38 for overlapping promoters and ability to support CRP activation. Nucleic Acids Res 23: 819–26.

38. SinghSS, GraingerDC (2013) H-NS can facilitate specific DNA-binding by RNA polymerase in AT-rich gene regulatory regions. PLoS Genet 9: e1003589.

39. BaileyTL, BodenM, BuskeFA, FrithM, GrantCE, et al. (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37 (Web Server issue) W202–8.

40. KimD, HongJS, QiuY, NagarajanH, SeoJH, et al. (2012) Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling. PLoS Genet 8 (8) e1002867.

41. ChoBK, KimD, KnightEM, ZenglerK, PalssonBØ (2014) Genome-scale reconstruction of the sigma factor network in Escherichia coli: topology and functional states. BMC Biol 12: 4.

42. HiardS, MareeR, ColsonS, HoskissonPA, TitgemeyerF, et al. (2007) PREDetector: A new tool to identify regulatory elements in bacterial genomes. Biochem Biophys Res Commun 357 (4) 861–4.

43. CarverT, ThomsonN, BleasbyA, BerrimanM, ParkhillJ (2009) DNAPlotter: circular and linear interactive genome visualization. Bioinformatics 25: 119–20.

44. SaveryNJ, LloydGS, KainzM, GaalT, RossW, et al. (1998) Transcription activation at Class II CRP-dependent promoters: identification of determinants in the C-terminal domain of the RNA polymerase alpha subunit. EMBO J 17: 3439–3447.

45. GraingerDC, GoldbergMD, LeeDJ, BusbySJ (2008) Selective repression by Fis and H-NS at the Escherichia coli dps promoter. Mol Microbiol 68: 1366–1377.

46. LloydGS, HollandsK, GodfreyRE, BusbySJ (2008) Transcription initiation in the Escherichia coli K-12 malI-malX intergenic region and the role of the cyclic AMP receptor protein. FEMS Microbiol Lett 288: 250–7.

47. Miller J (1972) Experiments in Molecular Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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