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Gastric antibacterial efficiency is different for pepsin A and C

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Abstract

The gastric lumen represents a bactericidal barrier, whose major components are an acidic pH and a family of isoenzymes of the gastric aspartate protease, pepsin. To evaluate whether specific pepsins are specialized in antibacterial protection, we tested their effects on the gastric pathogen Helicobacter pylori. In a recent study we found pepsin to affect the motility of the bacteria, one of its most important virulence factors. We were able to show that the antibacterial effect of pepsin occurs in two phases: rapid loss of motility and subsequent destruction. In the present study we used the rapid pepsin-induced bacterial immobilization as a marker of antibacterial efficiency. The proteolytic activity of different pepsins was normalized to values between 2 and 200 U/ml in the hemoglobin degradation test of Anson, performed at pH 2 and 5. We found that pepsin C completely inactivates H. pylori at proteolytic activities of 2 (pH 5) and 20 (pH 2) U/ml. In contrast, the activities of pepsin A and chymosin required to affect Helicobacter motility were ten times higher.

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References

  • Anson ML (1938) The estimation of pepsin, trypsin, papain, and cathepsin with hemoglobin. J Gen Physiol 22:79–89

    Article  CAS  PubMed  Google Scholar 

  • Barlow AP, Hinder RA, DeMeester TR, Fuchs K (1994) Twenty-four-hour gastric luminal pH in normal subjects: influence of probe position, food, posture, and duodenogastric reflux. Am J Gastroenterol 89:2006–2010

    PubMed  CAS  Google Scholar 

  • Becker T, Rapp W (1979a) Characterization of human pepsin II obtained from purified gastric pepsinogen II. Klin Wochenschr 57:719–724

    Article  CAS  Google Scholar 

  • Becker T, Rapp W (1979b) Characterization of human pepsin I obtained from purified gastric pepsinogen I. Klin Wochenschr 57:711–718

    Article  CAS  Google Scholar 

  • Dooley CP, Cohen H, Fitzgibbons PL, Bauer M, Appleman MD, Perez-Perez GI, Blaser MJ (1989) Prevalence of Helicobacter pylori infection and histologic gastritis in asymptomatic persons. N Engl J Med 321:1562–1566

    Article  PubMed  CAS  Google Scholar 

  • Dunn BM, Oda K, Kay J, Rao-Naik C, Lowther WT, Beyer BM, Scarborough PE, Bukhtiyarova M (1998) Comparison of the specificity of the aspartic proteinases towards internally consistent sets of oligopeptide substrates. Adv Exp Med Biol 436:133–138

    PubMed  CAS  Google Scholar 

  • Eaton KA, Suerbaum S, Josenhans C, Krakowka S (1996) Colonization of gnotobiotic piglets by Helicobacter pylori deficient in two flagellin genes. Infect Immun 64:2445–2448

    PubMed  CAS  Google Scholar 

  • Etherington DJ, Taylor WH (1967) Nomenclature of the pepsins. Nature 216:279–280

    Article  PubMed  CAS  Google Scholar 

  • Foltmann B (1992) Chymosin: a short review on foetal and neonatal gastric proteases. Scand J Clin Lab Invest Suppl 210:65–79

    Article  PubMed  CAS  Google Scholar 

  • Foltmann B (1966) A review on prorennin and rennin. C R Trav Lab Carlsberg 35:143–231

    PubMed  CAS  Google Scholar 

  • Foltmann B, Szecsi PB, Tarasova NI (1985) Detection of proteases by clotting of casein after gel electrophoresis. Anal Biochem 146:353–360

    Article  PubMed  CAS  Google Scholar 

  • Fruton JS (1970) The specificity and mechanism of pepsin action. Adv Enzymol Relat Areas Mol Biol 33:401–443

    Article  PubMed  CAS  Google Scholar 

  • Gregersen JP (1916) Untersuchungen über die antiseptische Wirkung des Magensaftes. Centralbl f Bakt ect Abt I Originale 77:353–361

    CAS  Google Scholar 

  • Hayano T, Sogawa K, Ichihara Y, Fujii-Kuriyama Y, Takahashi K (1988) Primary structure of human pepsinogen C gene. J Biol Chem 263:1382–1385

    PubMed  CAS  Google Scholar 

  • Herriott RM (1962) Pepsinogen and pepsin. J Gen Physiol 45:57–76

    Article  PubMed  CAS  Google Scholar 

  • Ishihara T, Ichihara Y, Hayano T, Katsura I, Sogawa K, Fujii-Kuriyama Y, Takahashi K (1989) Primary structure and transcriptional regulation of rat pepsinogen C gene. J Biol Chem 264:10193–10199

    PubMed  CAS  Google Scholar 

  • Josenhans C, Suerbaum S (2002) The role of motility as a virulence factor in bacteria. Int J Med Microbiol 291:605–614

    Article  PubMed  CAS  Google Scholar 

  • Kageyama T (2000) New world monkey pepsinogens A and C, and prochymosins. Purification, characterization of enzymatic properties, cDNA cloning, and molecular evolution. J Biochem (Tokyo) 127:761–770

    CAS  Google Scholar 

  • Kageyama T (2002) Pepsinogens, progastricsins and prochymosins: structure, function, evolution and development. Cell Mol Life Sci 59:288–306

    Article  PubMed  CAS  Google Scholar 

  • Kageyama T, Ichinose M, Tsukada-Kato S, Omata M, Narita Y, Moriyama A, Yonezawa S (2000) Molecular cloning of neonate/infant-specific pepsinogens from rat stomach mucosa and their expressional change during development. Biochem Biophys Res Commun 267:806–812

    Article  PubMed  CAS  Google Scholar 

  • Koch R (1884) Conferenz zur Erörterung der Cholerafrage. Berliner klinische Wochenschrift 21:Nr. 31 + 32

  • 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 

  • Megraud F, Brassens-Rabbe MP, Denis F, Belbouri A, Hoa DQ (1989) Seroepidemiology of Campylobacter pylori infection in various populations. J Clin Microbiol 27:1870–1873

    PubMed  CAS  Google Scholar 

  • Mitchell DJ, McClure BG, Tubman TR (2001) Simultaneous monitoring of gastric and oesophageal pH reveals limitations of conventional oesophageal pH monitoring in milk fed infants. Arch Dis Child 84:273–276

    Article  PubMed  CAS  Google Scholar 

  • Narita Y, Oda S, Moriyama A, Kageyama T (2002) Primary structure, unique enzymatic properties, and molecular evolution of pepsinogen B and pepsin B. Arch Biochem Biophys 404:177–185

    Article  PubMed  CAS  Google Scholar 

  • Narita Y, Oda S, Moriyama A, Takenaka O, Kageyama T (1997) Pepsinogens and pepsins from house musk shrew, Suncus murinus: purification, characterization, determination of the amino-acid sequences of the activation segments, and analysis of proteolytic specificities. J Biochem (Tokyo) 121:1010–1017

    CAS  Google Scholar 

  • Nielsen PK, Foltmann B (1995) Purification and characterization of porcine pepsinogen B and pepsin B. Arch Biochem Biophys 322:417–422

    Article  PubMed  CAS  Google Scholar 

  • Örd T, Kolmer M, Villems R, Saarma M (1990) Structure of the human genomic region homologous to the bovine prochymosin-encoding gene. Gene 91:241–246

    Article  PubMed  Google Scholar 

  • Ottemann KM, Lowenthal AC (2002) Helicobacter pylori uses motility for initial colonization and to attain robust infection. Infect Immun 70:1984–1990

    Article  PubMed  CAS  Google Scholar 

  • Pearson JP, Ward R, Allen A, Roberts NB, Taylor WH (1986) Mucus degradation by pepsin: comparison of mucolytic activity of human pepsin 1 and pepsin 3: implications in peptic ulceration. Gut 27:243–248

    Article  PubMed  CAS  Google Scholar 

  • Richter C, Tanaka T, Yada RY (1998) Mechanism of activation of the gastric aspartic proteinases: pepsinogen, progastricsin and prochymosin. Biochem J 335 ( Pt 3):481–490

    CAS  Google Scholar 

  • Samloff IM (1971) Cellular localization of group I pepsinogens in human gastric mucosa by immunofluorescence. Gastroenterology 61:185–188

    PubMed  CAS  Google Scholar 

  • Samloff IM, Liebman WM (1973) Cellular localization of the group II pepsinogens in human stomach and duodenum by immunofluorescence. Gastroenterology 65:36–42

    PubMed  CAS  Google Scholar 

  • Sano J, Miki K, Ichinose M, Kimura M, Kurokawa K, Aida T, Ishizaki M, Asano G, Masugi Y, Wong RN (1989) In situ localization of pepsinogens I and II mRNA in human gastric mucosa. Acta Pathol Jpn 39:765–771

    PubMed  CAS  Google Scholar 

  • Schreiber S, Bücker R, Groll C, Baptista M, Garten D, Scheid P, Friedrich S, Josenhans C, Suerbaum S (2005) Rapid loss of motility of Helicobacter pylori in the gastric lumen in vivo. Infect Immun 73:1584–1589

    Article  PubMed  CAS  Google Scholar 

  • Schreiber S, Konradt M, Groll C, Scheid P, Hanauer G, Werling HO, Josenhans C, Suerbaum S (2004) The spatial orientation of Helicobacter pylori in the gastric mucus. Proc Natl Acad Sci USA 101:5024–5029

    Article  PubMed  CAS  Google Scholar 

  • Schreiber S, Nguyen TH, Stüben M, Scheid P (2000) Demonstration of a pH gradient in the gastric gland of the acid-secreting guinea pig mucosa. Am J Physiol Gastrointest Liver Physiol 279:G597–G604

    PubMed  CAS  Google Scholar 

  • Schreiber S, Scheid P (1997) Gastric mucus of the guinea pig: proton carrier and diffusion barrier. Am J Physiol 272:G63–G70

    PubMed  CAS  Google Scholar 

  • Suerbaum S (1995) The complex flagella of gastric Helicobacter species. Trends Microbiol 3:168–161

    Article  PubMed  CAS  Google Scholar 

  • Suerbaum S, Michetti P (2002) Helicobacter pylori infection. N Engl J Med 347:1175–1186

    Article  PubMed  CAS  Google Scholar 

  • Waalewijn RA, Meuwissen SG, Pals G, Hoefsmit EC (1991) Localization of pepsinogen (A and C) and cellular differentiation of pepsinogen-synthesizing cells in the human gastric mucosa. Eur J Cell Biol 54:55–60

    PubMed  CAS  Google Scholar 

  • Zelle B, Evers MP, Groot PC, Bebelman JP, Mager WH, Planta RJ, Pronk JC, Meuwissen SG, Hofker MH, Eriksson AW (1988) Genomic structure and evolution of the human pepsinogen A multigene family. Hum Genet 78:79–82

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors thank Gabi Reimus and Jacqui Burton for excellent technical assistance. This study was supported by the grants Sche 46/14-1 and Su 133/4-1 from the Deutsche Forschungsgemeinschaft (DFG).

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Correspondence to Sören Schreiber.

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Schreiber, S., Bücker, R., Groll, C. et al. Gastric antibacterial efficiency is different for pepsin A and C. Arch Microbiol 184, 335–340 (2006). https://doi.org/10.1007/s00203-005-0053-9

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  • DOI: https://doi.org/10.1007/s00203-005-0053-9

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