Skip to main content
SpringerLink
Log in

Urea Transport in Bacteria: Acid Acclimation by Gastric Helicobacter spp

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

Urea transporters in bacteria are relatively rare. There are three classes, the ABC transporters such as those expressed by cyanobacteria and Corynebacterium glutamicum, the Yut protein expressed by Yersinia spp and the UreI expressed by gastric Helicobacter spp. This review focuses largely on the UreI proton-gated channel that is part of the acid acclimation mechanism essential for gastric colonization by the latter. UreI is a six-transmembrane polytopic integral membrane protein, N and C termini periplasmic, and is expressed in all gastric Helicobacter spp that have been studied but also in Helicobacter hepaticus and Streptococcus salivarius. The first two are proton-gated, the latter is pH insensitive. Site-directed mutagenesis and chimeric constructs have identified histidines and dicarboxylic amino acids in the second periplasmic loop of H. pylori and the first loop of H. hepaticus UreI and the C terminus of both as involved in a hydrogen-bonding dependence of proton gating, with the membrane domain in these but not in the UreI of S. salivarius responding to the periplasmic conformational changes. UreI and urease are essential for gastric colonization and urease associates with UreI during acid exposure, facilitating activation of the UreA and UreB apoenzyme complex by Ni2+ insertion by the UreF-UreH and UreE-UreG assembly proteins. Transcriptome analysis of acid responses of H. pylori also identified a cytoplasmic and periplasmic carbonic anhydrase as responding specifically to changes in periplasmic pH and these have been shown to be essential also for acid acclimation. The finding also of upregulation of the two-component histidine kinase HP0165 and its response element HP0166, illustrates the complexity of the acid acclimation processes involved in gastric colonization by this pathogen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  • Andrutis K.A., Fox J.G., Schauer D.B., Marini R.P., Murphy J.C., Yan L., Solnik J. 1995. Inability of an isogenic urease-negative mutant stain of Helicobacter mustelae to colonize the ferret stomach. Infect. Immun. 63:3722–3725

    PubMed  CAS  Google Scholar 

  • Athmann C., Zeng N., Kang T., Marcus E.A., Scott D.R., Rektorschek M., Buhmann A., Melchers K., Sachs G. 2000. Local pH elevation mediated by the intrabacterial urease of Helicobacter pylori cocultured with gastric cells. J. Clin. Invest. 106:339–347

    PubMed  CAS  Google Scholar 

  • Beckers G., Bendt A.K., Kramer R., Burkovski A. 2004. Molecular identification of the urea uptake system and transcriptional analysis of urea transporter- and urease-encoding genes in Corynebacterium glutamicum. J. Bacteriol. 186:7645–7652

    Article  PubMed  CAS  Google Scholar 

  • Brayman T.G., Hausinger R.P. 1996. Purification, characterization, and functional analysis of a truncated Klebsiella aerogenes UreE urease accessory protein lacking the histidine-rich carboxyl terminus. J. Bacteriol. 178:5410–5416

    PubMed  CAS  Google Scholar 

  • Bury-Mone S., Skouloubris S., Labigne A., De Reuse H. 2001. The Helicobacter pylori UreI protein: role in adaptation to acidity and identification of residues essential for its activity and for acid activation. Mol Microbiol. 42:1021–1034

    Article  PubMed  CAS  Google Scholar 

  • Chebrou H., Bigey F., Arnaud A., Galzy P. 1996. Amide metabolism: a putative ABC transporter in Rhodococcus sp. R312. Gene. 182:215–218

    Article  PubMed  CAS  Google Scholar 

  • Chen Y.Y., Weaver C.A., Mendelsohn D.R., Burne R.A. 1998. Transcriptional regulation of the Streptococcus salivarius 57.I urease operon. J. Bacteriol. 180:5769–5775

    PubMed  CAS  Google Scholar 

  • Chen Y.Y., Burne R.A. 2003. Identification and characterization of the nickel uptake system for urease biogenesis in Streptococcus salivarius 57.I. J. Bacteriol. 185:6773–6779

    Article  PubMed  CAS  Google Scholar 

  • Colpas G.J., Brayman T.G., Ming L.J., Hausinger R.P. 1999. Identification of metal-binding residues in the Klebsiella aerogenes urease nickel metallochaperone, UreE. Biochemistry. 38:4078–4088

    Article  PubMed  CAS  Google Scholar 

  • de Koning-Ward T.F., Robins-Browne R.M. 1997. A novel mechanism of urease regulation in Yersinia enterocolitica. FEMS Microbiol. Lett. 147:221–226

    Article  PubMed  Google Scholar 

  • Eaton K.A., Krakowka S. 1994. Effect of gastric pH on urease-dependent colonization of gnotobiotic piglets by Helicobacter pylori. Infect. Immun. 62:3604–3607

    PubMed  CAS  Google Scholar 

  • Flores E., Herrero A. 2005. Nitrogen assimilation and nitrogen control in cyanobacteria. Aliment. Pharmacol. Ther. 16:533–544

    Google Scholar 

  • Foster J.W. 2004. Escherichia coli acid resistance: tales of an amateur acidophile. Nat. Rev. Microbiol. 2:898–907

    Article  PubMed  CAS  Google Scholar 

  • Goodman B. 2002. Transport of small molecules across cell membranes water channels and urea transporters. Adv. Physiol. Educ. 26:146–157

    PubMed  Google Scholar 

  • Hediger M.A., Smith C.P., You G., Lee W.S., Kanai Y., Shayakul C. 1996. Structure, regulation and physiological roles of urea transporters. Kidney Intern. 49:1615–1623

    CAS  Google Scholar 

  • Hong W., Sano K., Morimatsu S., Scott D.R., Weeks D.L., Sachs G., Goto T., Mohan S., Harada F., Nakajima N., Nakano T. 2003. Medium pH-dependent redistribution of the urease of Helicobacter pylori. J. Med. Microbiol. 52:211–216

    Article  PubMed  CAS  Google Scholar 

  • Jahns T., Zobel A., Kleiner D., Kaltwasser H. 1988. Evidence for carrier-mediated, energy-dependent uptake of urea in some bacteria. Arch. Microbiol. 149:377–383

    Article  CAS  Google Scholar 

  • Lee Y.-C., Takata T., Shan H.Y., Grandjean B., Charney A.N., Ando T., Perez-Perez G.I., Blaser M. 2002. The carbonic anhydrase genes of Helicobacter pylori: characteristics and biological roles. Gastroenterol. 122 suppl:A423

    Google Scholar 

  • Labigne A., Cussac V., Courcoux P. 1991. Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J. Bacteriol. 173:1920–1931

    PubMed  CAS  Google Scholar 

  • Magaña-Plaza I., Ruiz-Herrera J. 1967. Mechanisms of regulation of urease biosynthesis in Proteus rettgeri. J. Bacteriol. 93:1294–1301

    PubMed  Google Scholar 

  • Marcus E.A., Moshfegh A.P., Sachs G., Scott D.R. 2005. The periplasmic alpha-carbonic anhydrase activity of Helicobacter pylori is essential for acid acclimation. J. Bacteriol. 187:729–738

    Article  PubMed  CAS  Google Scholar 

  • Mathai J.C. 2005. Ammonotelic teleosts and urea transporters. Am. J. Physiol. 288:F453–454

    Article  CAS  Google Scholar 

  • Mayrand R.R., Levitt D.G. 1983. Urea and ethylene Glycol facilitated transport systems in the human red cell membrane: saturation, competition, and asymmetry. J. Gen. Physiol. 81:221–237

    Article  PubMed  CAS  Google Scholar 

  • Meyer-Rosberg K., Scott D.R., Rex D., Melchers K., Sachs G. 1996. The effect of environmental pH on the proton motive force of Helicobacter pylori. Gastroenterology. 111:886–900

    Article  PubMed  CAS  Google Scholar 

  • Mills J., Wyborn N.R., Greenwood J.A., Williams S.G., Jones C.W. 1998. Characterisation of a binding-protein-dependent, active transport system for short-chain amides and urea in the methylotrophic bacterium Methylophilus methylotrophus. Eur. J. Biochem. 251:45–53

    Article  PubMed  CAS  Google Scholar 

  • Mobley H.L., Island M.D., Hausinger R.P. 1995. Molecular biology of microbial ureases. Microbiol. Rev. 59:451–480

    PubMed  CAS  Google Scholar 

  • Mollenhauer-Rektorschek M., Hanauer G., Sachs G., Melchers K. 2002. Expression of UreI is required for intragastric transit and colonization of gerbil gastric mucosa by Helicobacter pylori. Res. Microbiol. 153: 659–666

    Article  PubMed  CAS  Google Scholar 

  • Moncrief M.B., Hausinger R.P. 1997. Characterization of UreG, identification of a UreD-UreF-UreG complex, and evidence suggesting that a nucleotide-binding site in UreG is required for in vivo metallocenter assembly of Klebsiella aerogenes urease. J. Bacteriol. 179: 4081–4086

    PubMed  CAS  Google Scholar 

  • Moncrief M.B., Hausinger R.P. 1996. Purification and activation properties of UreD-UreF-urease apoprotein complexes. J. Bacteriol 178:5417–5421

    PubMed  CAS  Google Scholar 

  • Mulrooney S.B., Hausinger R.P. 1990. Sequence of the Klebsiella aerogenes urease genes and evidence for accessory proteins facilitating nickel incorporation. J. Bacteriol. 172:5837–5843

    PubMed  CAS  Google Scholar 

  • Nielsen S., Froklaer J., Marples D., Kwon T.H., Agre P., Knepper M.A. 2002. Aquaporins in the kidney: from molecules to medicine. Physiol. Rev. 82:205–244

    PubMed  CAS  Google Scholar 

  • Olives B., Neau P., Bailly P., Hediger M.A., Rousselet G., Cartron J.P., Ripoche P. 1994. Cloning and functional expression of a urea transporter from human bone marrow cells. J. Biol. Chem. 269:31649–31652

    PubMed  CAS  Google Scholar 

  • Rektorschek M., Weeks D., Sachs G., Melchers K. 1998. Influence of pH on metabolism and urease activity of Helicobacter pylori. Gastroenterology. 115:628–641

    Article  PubMed  CAS  Google Scholar 

  • Sands J.M. 1999. Urea transport: It’s not just “freely diffusible” anymore. TIPS 14:46–47

    Google Scholar 

  • Sands J.M. 2003. Mammalian urea transporters Annu. Rev. Physiol. 65:543–566

    Article  PubMed  CAS  Google Scholar 

  • Sands J.M. 2004. Renal Urea transporters Curr. Opinion. Nephrol. Hypert. 13:525–532

    Article  CAS  Google Scholar 

  • Sands J.M., Nonoguchi H., Knepper M.A. 1987. Vasopressin effects on urea and H2O transport in inner medullary collecting duct subsegments. Am. J. Physiol. 253:F823–F832

    PubMed  CAS  Google Scholar 

  • Schar J., Sickmann A., Beier D. 2005. Phosphorylation-independent activity of atypical response regulators of Helicobacter pylori. J. Bacteriol. 187:3100–3109

    Article  PubMed  CAS  Google Scholar 

  • Scott D.R., Marcus E.A., Weeks D.L., Sachs G. 2002. Mechanisms of acid resistance due to the urease system of Helicobacter pylori. Gastroenterology. 123:187–195

    Article  PubMed  CAS  Google Scholar 

  • Scott D.R., Marcus E.A., Weeks D.L., Lee A., Melchers K., Sachs G. 2000. Expression of the Helicobacter pylori ureI gene is required for acidic pH activation of cytoplasmic urease. Infect. Immun. 68:470–477

    Article  PubMed  CAS  Google Scholar 

  • Scott D.R., Weeks D., Hong C., Postius S., Melchers K., Sachs G. 1998. The role of internal urease in acid resistance of Helicobacter pylori. Gastroenterology. 114:58–70

    Article  PubMed  CAS  Google Scholar 

  • Sebbane F., Bury-Mone S., Cailliau K., Browaeys-Poly E., De Reuse H., Simonet M. 2002. The Yersinia pseudotuberculosis Yut protein, a new type of urea transporter homologous to eukaryotic channels and functionally interchangeable in vitro with the Helicobacter pylori UreI protein. Mol. Microbiol. 45:1165–1174

    Article  PubMed  CAS  Google Scholar 

  • Shayakul C., Hediger M.A. 2004. The SLC14 gene family of urea transporters. Pluegers Arch. 447:603–609

    Article  CAS  Google Scholar 

  • Siewe R.M., Weil B., Burkovski A., Eggeling L., Kramer R., Jahns T. 1998. Urea uptake and urease activity in Corynebacterium glutamicum. Arch. Microbiol. 169:411–416

    Article  PubMed  CAS  Google Scholar 

  • Skouloubris S., Thiberge J.M., Labigne A., De Reuse H. 1998. The Helicobacter pylori UreI protein is not involved in urease activity but is essential for bacterial survival in vivo. Infect. Immun. 66:4517–4521

    PubMed  CAS  Google Scholar 

  • Tien H.T. 1974. Bilayer lipid membranes. Dekker, New York

    Google Scholar 

  • Tsuda M., Karita M., Morshed M.G., Okita K., Nakazawa T. 1994. A urease-negative mutant of Helicobacter pylori constructed by allelic exchange mutagenesis lacks the ability to colonize the nude mouse stomach. Infect. Immun. 62:3586–3589

    PubMed  CAS  Google Scholar 

  • Valladares A., Montesinos M.L., Herrero A., Flores E. 2002. An ABC-type, high-affinity urea permease identified in cyanobacteria. Mol. Microbiol. 43:703–715

    Article  PubMed  CAS  Google Scholar 

  • Vanholder R., Glorieux G., Lameire G. 2005. New Insights in Uremic Toxicity. Contribut. Nephrol. 149:315–324

    Article  CAS  Google Scholar 

  • Voland P., Weeks D.L., Marcus E.A., Prinz C., Sachs G., Scott D. 2003. Interactions among the seven Helicobacter pylori proteins encoded by the urease gene cluster. Am. J. Physiol. 284:G96–G106

    CAS  Google Scholar 

  • Weeks D.L. 2001. Sites of pH regulation of the urea channel of Helicobacter pylori. Mol. Microbiol. 40:1249–1259

    Article  PubMed  CAS  Google Scholar 

  • Weeks D.L., Eskandari S., Scott D.R., Sachs G. 2000. A H+-gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Science 287:482–485

    Article  PubMed  CAS  Google Scholar 

  • Weeks D.L., Gushansky G., Scott D.R., Sachs G. 2004. Mechanism of proton gating of a urea channel. J. Biol. Chem. 279:9944–9950

    Article  PubMed  CAS  Google Scholar 

  • Wen Y., Marcus E.A., Matrubutham U., Gleeson M.A., Scott D.R., Sachs G. 2003. Acid-adaptive genes of Helicobacter pylori. Infect. Immun. 71:5921–5939

    Article  PubMed  CAS  Google Scholar 

  • Wen Y., Feng J., Scott D.R., Marcus E.A., Sachs G. 2006. Involvement of the HP0165-HP0166 two-component system in expression of some acidic-pH-upregulated genes of Helicobacter pylori. J. Bacteriol. 188:1750–1761

    Article  PubMed  CAS  Google Scholar 

  • Wilson S.A., Williams R.J., Pearl L.H., Drew R.E. 1995. Identification of two new genes in the Pseudomonas aeruginosa amidase operon, encoding an ATPase (AmiB) and a putative integral membrane protein (AmiS). J. Biol. Chem. 270:18818–18824

    Article  PubMed  CAS  Google Scholar 

  • Williams C.L., Preston T., Hossack M., Slater C., McColl K.E. 1996. Helicobacter pylori utilises urea for amino acid synthesis. FEMS Immunol. Med. Microbiol. 13:87–94

    Article  PubMed  CAS  Google Scholar 

  • Young G.M., Amid D., Miller V.L. 1996. A bifunctional urease enhances survival of pathogenic Yersinia enterocolitica and Morganella morganii at low pH. J. Bacteriol. 78: 6487–6495

    Google Scholar 

Download references

Acknowledgements

Our thanks are due to our long-time collaborators, Drs. David L. Weeks, Elizabeth A. Marcus and Klaus Melchers. Supported in part by U.S. Veterans Administration and NIH grant #’s DK46917, 53462 and 58333

Author information

Authors and Affiliations

  1. Department of Physiology, Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90073, USA

    G. Sachs, Y. Wen, J. Feng & D.R. Scott

  2. Department of Nephrology, David Geffen School of Medicine, UCLA and VA GLAHS, Los Angeles, CA, 90073, USA

    J.A. Kraut

Authors
  1. G. Sachs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J.A. Kraut
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D.R. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D.R. Scott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sachs, G., Kraut, J., Wen, Y. et al. Urea Transport in Bacteria: Acid Acclimation by Gastric Helicobacter spp . J Membrane Biol 212, 71–82 (2006). https://doi.org/10.1007/s00232-006-0867-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-006-0867-7

Keywords

Search

Navigation