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Structure of GrlR-GrlA complex that prevents GrlA activation of virulence genes.

Padavannil A, Jobichen C, Mills E, Velazquez-Campoy A, Li M, Leung KY, Mok YK, Rosenshine I, Sivaraman J
Nat Commun 4 2546 (2013)
Cited: 28 times
EuropePMC logo PMID: 24092262

Abstract

The locus of enterocyte effacement (LEE) is essential for virulence of enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). The 41 genes of the LEE encode type III secretion system proteins and three associated regulators: Ler, GrlA and GrlR. Ler is a positive regulator for most of the LEE operons, including grlRA. GrlA controls the expression of ler, ehxCABD and flhDC operons. GrlR binds to GrlA and suppresses its function. Here we report the crystal structure of GrlR-GrlAΔ (aa 1-106) complex (2:1) and its functional characterization. We show that GrlR interacts with the Helix-Turn-Helix motif of GrlA. Moreover, GrlA binds to the promoter DNA fragments of ler, ehxCABD and flhDC, and GrlR outcompetes with these promoter DNA sequences for the Helix-Turn-Helix motif of GrlA. These findings provide mechanistic insight into a regulatory module for the virulence of EPEC and EHEC, two important pathogens that cause devastating diseases.

Articles - 4kt5 mentioned but not cited (1)

  1. Bile salt receptor complex activates a pathogenic type III secretion system. Li P, Rivera-Cancel G, Kinch LN, Salomon D, Tomchick DR, Grishin NV, Orth K. Elife 5 e15718 (2016)


Reviews citing this publication (7)

  1. Type Three Secretion System in Attaching and Effacing Pathogens. Gaytán MO, Martínez-Santos VI, Soto E, González-Pedrajo B. Front Cell Infect Microbiol 6 129 (2016)
  2. Regulation of the Locus of Enterocyte Effacement in Attaching and Effacing Pathogens. Furniss RCD, Clements A. J Bacteriol 200 e00336-17 (2018)
  3. From ingestion to colonization: the influence of the host environment on regulation of the LEE encoded type III secretion system in enterohaemorrhagic Escherichia coli. Connolly JP, Finlay BB, Roe AJ. Front Microbiol 6 568 (2015)
  4. Environment Controls LEE Regulation in Enteropathogenic Escherichia coli. Platenkamp A, Mellies JL. Front Microbiol 9 1694 (2018)
  5. Control freaks-signals and cues governing the regulation of virulence in attaching and effacing pathogens. Turner NCA, Connolly JPR, Roe AJ. Biochem Soc Trans 47 229-238 (2019)
  6. Staying out or Going in? The Interplay between Type 3 and Type 5 Secretion Systems in Adhesion and Invasion of Enterobacterial Pathogens. Whelan R, McVicker G, Leo JC. Int J Mol Sci 21 E4102 (2020)
  7. Genomic island-encoded regulatory proteins in enterohemorrhagic Escherichia coli O157:H7. Wang F, Sun H, Kang C, Yan J, Chen J, Feng X, Yang B. Virulence 15 2313407 (2024)

Articles citing this publication (20)

  1. Host attachment and fluid shear are integrated into a mechanical signal regulating virulence in Escherichia coli O157:H7. Alsharif G, Ahmad S, Islam MS, Shah R, Busby SJ, Krachler AM. Proc Natl Acad Sci U S A 112 5503-5508 (2015)
  2. A long-term epigenetic memory switch controls bacterial virulence bimodality. Ronin I, Katsowich N, Rosenshine I, Balaban NQ. Elife 6 e19599 (2017)
  3. Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells. Ruano-Gallego D, Álvarez B, Fernández LÁ. ACS Synth Biol 4 1030-1041 (2015)
  4. Enterohaemorrhagic Escherichia coli produces outer membrane vesicles as an active defence system against antimicrobial peptide LL-37. Urashima A, Sanou A, Yen H, Tobe T. Cell Microbiol 19 (2017)
  5. Dynamics of expression and maturation of the type III secretion system of enteropathogenic Escherichia coli. Yerushalmi G, Litvak Y, Gur-Arie L, Rosenshine I. J Bacteriol 196 2798-2806 (2014)
  6. Hfq and three Hfq-dependent small regulatory RNAs-MgrR, RyhB and McaS-coregulate the locus of enterocyte effacement in enteropathogenic Escherichia coli. Bhatt S, Egan M, Ramirez J, Xander C, Jenkins V, Muche S, El-Fenej J, Palmer J, Mason E, Storm E, Buerkert T. Pathog Dis 75 ftw113 (2017)
  7. Virulence-related O islands in enterohemorrhagic Escherichia coli O157:H7. Jiang L, Yang W, Jiang X, Yao T, Wang L, Yang B. Gut Microbes 13 1992237 (2021)
  8. Lambda Red-mediated Recombineering in the Attaching and Effacing Pathogen Escherichia albertii. Egan M, Ramirez J, Xander C, Upreti C, Bhatt S. Biol Proced Online 18 3 (2016)
  9. LysR-type transcriptional regulator OvrB encoded in O island 9 drives enterohemorrhagic Escherichia coli O157:H7 virulence. Liu Y, Liu B, Yang P, Wang T, Chang Z, Wang J, Wang Q, Li W, Wu J, Huang D, Jiang L, Yang B. Virulence 10 783-792 (2019)
  10. RstA, a two-component response regulator, plays important roles in multiple virulence-associated processes in enterohemorrhagic Escherichia coli O157:H7. Liu Y, Li S, Li W, Wang P, Ding P, Li L, Wang J, Yang P, Wang Q, Xu T, Xiong Y, Yang B. Gut Pathog 11 53 (2019)
  11. The E. coli transcription factor GrlA is regulated by subcellular compartmentalization and activated in response to mechanical stimuli. Sirisaengtaksin N, Odem MA, Bosserman RE, Flores EM, Krachler AM. Proc Natl Acad Sci U S A 117 9519-9528 (2020)
  12. Bacterial-Chromatin Structural Proteins Regulate the Bimodal Expression of the Locus of Enterocyte Effacement (LEE) Pathogenicity Island in Enteropathogenic Escherichia coli. Leh H, Khodr A, Bouger MC, Sclavi B, Rimsky S, Bury-Moné S. mBio 8 e00773-17 (2017)
  13. Mechanosensing regulates virulence in Escherichia coli O157:H7. Islam MS, Krachler AM. Gut Microbes 7 63-67 (2016)
  14. GrlR, a negative regulator in enteropathogenic E. coli, also represses the expression of LEE virulence genes independently of its interaction with its cognate partner GrlA. Lara-Ochoa C, Huerta-Saquero A, Medrano-López A, Deng W, Finlay BB, Martínez-Laguna Y, Puente JL. Front Microbiol 14 1063368 (2023)
  15. Genomic analysis of shiga toxin-containing Escherichia coli O157:H7 isolated from Argentinean cattle. Amadio A, Bono JL, Irazoqui M, Larzábal M, Marques da Silva W, Eberhardt MF, Riviere NA, Gally D, Manning SD, Cataldi A. PLoS One 16 e0258753 (2021)
  16. High variation across E. coli hybrid isolates identified in metabolism-related biological pathways co-expressed with virulent genes. Gomes R, Denison Kroschel A, Day S, Jansen R. Gut Microbes 15 2228042 (2023)
  17. Optimization of type 3 protein secretion in enteropathogenic Escherichia coli. Yuan B, Economou A, Karamanou S. FEMS Microbiol Lett 365 (2018)
  18. Comparative genome and evolution analysis of the locus of enterocyte effacement from enteropathogenic Escherichia coli Deng and its transcriptional response to ciprofloxacin. Chen Z, Cheng H, Pan W, Zheng J, Li D, Lin F, Yu Z, Deng Q. J Med Microbiol 67 1368-1382 (2018)
  19. Screening of Anti-Adhesion Agents for Pathogenic Escherichia coli O157:H7 by Targeting the GrlA Activator. Hong SY, Kim BS. J Microbiol Biotechnol 33 329-338 (2023)
  20. The two sRNAs OmrA and OmrB indirectly repress transcription from the LEE1 promoter of enteropathogenic Escherichia coli. Muche S, El-Fenej J, Mihaita A, Mrozek Z, Cleary S, Critelli B, Marino M, Yu W, Amos B, Hunter T, Riga M, Buerkert T, Bhatt S. Folia Microbiol (Praha) 68 415-430 (2023)


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