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Published in: Gut Pathogens 1/2019

Open Access 01-12-2019 | Helicobacter Pylori | Research

Genome-wide mutation analysis of Helicobacter pylori after inoculation to Mongolian gerbils

Authors: Rumiko Suzuki, Kazuhito Satou, Akino Shiroma, Makiko Shimoji, Kuniko Teruya, Takashi Matsumoto, Junko Akada, Takashi Hirano, Yoshio Yamaoka

Published in: Gut Pathogens | Issue 1/2019

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Abstract

Background

Helicobacter pylori is a pathogenic bacterium that causes various gastrointestinal diseases in the human stomach. H. pylori is well adapted to the human stomach but does not easily infect other animals. As a model animal, Mongolian gerbils are often used, however, the genome of the inoculated H. pylori may accumulate mutations to adapt to the new host. To investigate mutations occurring in H. pylori after infection in Mongolian gerbils, we compared the whole genome sequence of TN2 wild type strain (TN2wt) and next generation sequencing data of retrieved strains from the animals after different lengths of infection.

Results

We identified mutations in 21 loci of 17 genes of the post-inoculation strains. Of the 17 genes, five were outer membrane proteins that potentially influence on the colonization and inflammation. Missense and nonsense mutations were observed in 15 and 6 loci, respectively. Multiple mutations were observed in three genes. Mutated genes included babA, tlpB, and gltS, which are known to be associated with adaptation to murine. Other mutations were involved with chemoreceptor, pH regulator, and outer membrane proteins, which also have potential to influence on the adaptation to the new host.

Conclusions

We confirmed mutations in genes previously reported to be associated with adaptation to Mongolian gerbils. We also listed up genes that mutated during the infection to the gerbils, though it needs experiments to prove the influence on adaptation.
Literature
1.
go back to reference Cover TL, Blaser MJ. Helicobacter pylori in health and disease. Gastroenterology. 2009;136(6):1863–73.CrossRef Cover TL, Blaser MJ. Helicobacter pylori in health and disease. Gastroenterology. 2009;136(6):1863–73.CrossRef
2.
go back to reference Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol. 2000;54:615–40.CrossRef Ernst PB, Gold BD. The disease spectrum of Helicobacter pylori: the immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu Rev Microbiol. 2000;54:615–40.CrossRef
3.
go back to reference Basso D, Plebani M, Kusters JG. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2010;15(Suppl 1):14–20.CrossRef Basso D, Plebani M, Kusters JG. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2010;15(Suppl 1):14–20.CrossRef
4.
go back to reference Yamaoka Y, Graham DY. Helicobacter pylori virulence and cancer pathogenesis. Future Oncol. 2014;10(8):1487–500.CrossRef Yamaoka Y, Graham DY. Helicobacter pylori virulence and cancer pathogenesis. Future Oncol. 2014;10(8):1487–500.CrossRef
5.
go back to reference Linz B, Windsor HM, Gajewski JP, Hake CM, Drautz DI, Schuster SC, Marshall BJ. Helicobacter pylori genomic microevolution during naturally occurring transmission between adults. PLoS ONE. 2013;8(12):e82187.CrossRef Linz B, Windsor HM, Gajewski JP, Hake CM, Drautz DI, Schuster SC, Marshall BJ. Helicobacter pylori genomic microevolution during naturally occurring transmission between adults. PLoS ONE. 2013;8(12):e82187.CrossRef
6.
go back to reference Linz B, Windsor HM, McGraw JJ, Hansen LM, Gajewski JP, Tomsho LP, Hake CM, Solnick JV, Schuster SC, Marshall BJ. A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques. Nat Commun. 2014;5:4165.CrossRef Linz B, Windsor HM, McGraw JJ, Hansen LM, Gajewski JP, Tomsho LP, Hake CM, Solnick JV, Schuster SC, Marshall BJ. A mutation burst during the acute phase of Helicobacter pylori infection in humans and rhesus macaques. Nat Commun. 2014;5:4165.CrossRef
7.
go back to reference Kennemann L, Didelot X, Aebischer T, Kuhn S, Drescher B, Droege M, Reinhardt R, Correa P, Meyer TF, Josenhans C, et al. Helicobacter pylori genome evolution during human infection. Proc Natl Acad Sci USA. 2011;108(12):5033–8.CrossRef Kennemann L, Didelot X, Aebischer T, Kuhn S, Drescher B, Droege M, Reinhardt R, Correa P, Meyer TF, Josenhans C, et al. Helicobacter pylori genome evolution during human infection. Proc Natl Acad Sci USA. 2011;108(12):5033–8.CrossRef
8.
go back to reference Didelot X, Nell S, Yang I, Woltemate S, van der Merwe S, Suerbaum S. Genomic evolution and transmission of Helicobacter pylori in two South African families. Proc Natl Acad Sci USA. 2013;110(34):13880–5.CrossRef Didelot X, Nell S, Yang I, Woltemate S, van der Merwe S, Suerbaum S. Genomic evolution and transmission of Helicobacter pylori in two South African families. Proc Natl Acad Sci USA. 2013;110(34):13880–5.CrossRef
9.
go back to reference Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M. Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci USA. 2004;101(7):2106–11.CrossRef Solnick JV, Hansen LM, Salama NR, Boonjakuakul JK, Syvanen M. Modification of Helicobacter pylori outer membrane protein expression during experimental infection of rhesus macaques. Proc Natl Acad Sci USA. 2004;101(7):2106–11.CrossRef
10.
go back to reference Yamaoka Y, Kita M, Kodama T, Imamura S, Ohno T, Sawai N, Ishimaru A, Imanishi J, Graham DY. Helicobacter pylori infection in mice: role of outer membrane proteins in colonization and inflammation. Gastroenterology. 2002;123(6):1992–2004.CrossRef Yamaoka Y, Kita M, Kodama T, Imamura S, Ohno T, Sawai N, Ishimaru A, Imanishi J, Graham DY. Helicobacter pylori infection in mice: role of outer membrane proteins in colonization and inflammation. Gastroenterology. 2002;123(6):1992–2004.CrossRef
11.
go back to reference Styer CM, Hansen LM, Cooke CL, Gundersen AM, Choi SS, Berg DE, Benghezal M, Marshall BJ, Peek RM Jr, Boren T, et al. Expression of the BabA adhesin during experimental infection with Helicobacter pylori. Infect Immun. 2010;78(4):1593–600.CrossRef Styer CM, Hansen LM, Cooke CL, Gundersen AM, Choi SS, Berg DE, Benghezal M, Marshall BJ, Peek RM Jr, Boren T, et al. Expression of the BabA adhesin during experimental infection with Helicobacter pylori. Infect Immun. 2010;78(4):1593–600.CrossRef
12.
go back to reference Ohno T, Vallstrom A, Rugge M, Ota H, Graham DY, Arnqvist A, Yamaoka Y. Effects of blood group antigen-binding adhesin expression during Helicobacter pylori infection of Mongolian gerbils. J Infect Dis. 2011;203(5):726–35.CrossRef Ohno T, Vallstrom A, Rugge M, Ota H, Graham DY, Arnqvist A, Yamaoka Y. Effects of blood group antigen-binding adhesin expression during Helicobacter pylori infection of Mongolian gerbils. J Infect Dis. 2011;203(5):726–35.CrossRef
13.
go back to reference Hirayama F, Takagi S, Yokoyama Y, Iwao E, Ikeda Y. Establishment of gastric Helicobacter pylori infection in Mongolian gerbils. J Gastroenterol. 1996;31(Suppl 9):24–8.PubMed Hirayama F, Takagi S, Yokoyama Y, Iwao E, Ikeda Y. Establishment of gastric Helicobacter pylori infection in Mongolian gerbils. J Gastroenterol. 1996;31(Suppl 9):24–8.PubMed
14.
go back to reference Ikeno T, Ota H, Sugiyama A, Ishida K, Katsuyama T, Genta RM, Kawasaki S. Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils. Am J Pathol. 1999;154(3):951–60.CrossRef Ikeno T, Ota H, Sugiyama A, Ishida K, Katsuyama T, Genta RM, Kawasaki S. Helicobacter pylori-induced chronic active gastritis, intestinal metaplasia, and gastric ulcer in Mongolian gerbils. Am J Pathol. 1999;154(3):951–60.CrossRef
15.
go back to reference Ogura K, Maeda S, Nakao M, Watanabe T, Tada M, Kyutoku T, Yoshida H, Shiratori Y, Omata M. Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil. J Exp Med. 2000;192(11):1601–10.CrossRef Ogura K, Maeda S, Nakao M, Watanabe T, Tada M, Kyutoku T, Yoshida H, Shiratori Y, Omata M. Virulence factors of Helicobacter pylori responsible for gastric diseases in Mongolian gerbil. J Exp Med. 2000;192(11):1601–10.CrossRef
16.
go back to reference Beckett AC, Loh JT, Chopra A, Leary S, Lin AS, McDonnell WJ, Dixon B, Noto JM, Israel DA, Peek RM Jr, et al. Helicobacter pylori genetic diversification in the Mongolian gerbil model. PeerJ. 2018;6:e4803.CrossRef Beckett AC, Loh JT, Chopra A, Leary S, Lin AS, McDonnell WJ, Dixon B, Noto JM, Israel DA, Peek RM Jr, et al. Helicobacter pylori genetic diversification in the Mongolian gerbil model. PeerJ. 2018;6:e4803.CrossRef
17.
go back to reference Behrens W, Schweinitzer T, Bal J, Dorsch M, Bleich A, Kops F, Brenneke B, Didelot X, Suerbaum S, Josenhans C. Role of energy sensor TlpD of Helicobacter pylori in gerbil colonization and genome analyses after adaptation in the gerbil. Infect Immun. 2013;81(10):3534–51.CrossRef Behrens W, Schweinitzer T, Bal J, Dorsch M, Bleich A, Kops F, Brenneke B, Didelot X, Suerbaum S, Josenhans C. Role of energy sensor TlpD of Helicobacter pylori in gerbil colonization and genome analyses after adaptation in the gerbil. Infect Immun. 2013;81(10):3534–51.CrossRef
18.
go back to reference Harris AG, Wilson JE, Danon SJ, Dixon MF, Donegan K, Hazell SL. Catalase (KatA) and KatA-associated protein (KapA) are essential to persistent colonization in the Helicobacter pylori SS1 mouse model. Microbiology. 2003;149(Pt 3):665–72.CrossRef Harris AG, Wilson JE, Danon SJ, Dixon MF, Donegan K, Hazell SL. Catalase (KatA) and KatA-associated protein (KapA) are essential to persistent colonization in the Helicobacter pylori SS1 mouse model. Microbiology. 2003;149(Pt 3):665–72.CrossRef
20.
go back to reference Noto JM, Gaddy JA, Lee JY, Piazuelo MB, Friedman DB, Colvin DC, Romero-Gallo J, Suarez G, Loh J, Slaughter JC, et al. Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans. J Clin Invest. 2013;123(1):479–92.CrossRef Noto JM, Gaddy JA, Lee JY, Piazuelo MB, Friedman DB, Colvin DC, Romero-Gallo J, Suarez G, Loh J, Slaughter JC, et al. Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans. J Clin Invest. 2013;123(1):479–92.CrossRef
21.
go back to reference Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M. Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology. 1998;115(3):642–8.CrossRef Watanabe T, Tada M, Nagai H, Sasaki S, Nakao M. Helicobacter pylori infection induces gastric cancer in mongolian gerbils. Gastroenterology. 1998;115(3):642–8.CrossRef
22.
go back to reference Sugimoto M, Ohno T, Graham DY, Yamaoka Y. Helicobacter pylori outer membrane proteins on gastric mucosal interleukin 6 and 11 expression in Mongolian gerbils. J Gastroenterol Hepatol. 2011;26(11):1677–84.CrossRef Sugimoto M, Ohno T, Graham DY, Yamaoka Y. Helicobacter pylori outer membrane proteins on gastric mucosal interleukin 6 and 11 expression in Mongolian gerbils. J Gastroenterol Hepatol. 2011;26(11):1677–84.CrossRef
23.
go back to reference Chin CS, Alexander DH, Marks P, Klammer AA, Drake J, Heiner C, Clum A, Copeland A, Huddleston J, Eichler EE, et al. Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data. Nat Methods. 2013;10(6):563–9.CrossRef Chin CS, Alexander DH, Marks P, Klammer AA, Drake J, Heiner C, Clum A, Copeland A, Huddleston J, Eichler EE, et al. Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data. Nat Methods. 2013;10(6):563–9.CrossRef
24.
go back to reference Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235–42.CrossRef Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res. 2000;28(1):235–42.CrossRef
25.
go back to reference Burley SK, Berman HM, Bhikadiya C, Bi C, Chen L, Di Costanzo L, Christie C, Dalenberg K, Duarte JM, Dutta S, et al. RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Res. 2019;47(D1):D464–D474474.CrossRef Burley SK, Berman HM, Bhikadiya C, Bi C, Chen L, Di Costanzo L, Christie C, Dalenberg K, Duarte JM, Dutta S, et al. RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Res. 2019;47(D1):D464–D474474.CrossRef
26.
go back to reference Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12.CrossRef Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–12.CrossRef
27.
go back to reference Healy J, Ekkerman S, Pliotas C, Richard M, Bartlett W, Grayer SC, Morris GM, Miller S, Booth IR, Conway SJ, et al. Understanding the structural requirements for activators of the Kef bacterial potassium efflux system. Biochemistry. 2014;53(12):1982–92.CrossRef Healy J, Ekkerman S, Pliotas C, Richard M, Bartlett W, Grayer SC, Morris GM, Miller S, Booth IR, Conway SJ, et al. Understanding the structural requirements for activators of the Kef bacterial potassium efflux system. Biochemistry. 2014;53(12):1982–92.CrossRef
28.
go back to reference Skouloubris S, Thiberge JM, Labigne A, De Reuse H. The Helicobacter pylori UreI protein is not involved in urease activity but is essential for bacterial survival in vivo. Infect Immun. 1998;66(9):4517–21.PubMedPubMedCentral Skouloubris S, Thiberge JM, Labigne A, De Reuse H. The Helicobacter pylori UreI protein is not involved in urease activity but is essential for bacterial survival in vivo. Infect Immun. 1998;66(9):4517–21.PubMedPubMedCentral
29.
go back to reference Scott D, Weeks D, Melchers K, Sachs G. UreI-mediated urea transport in Helicobacter pylori: an open and shut case? Trends Microbiol. 2000;8(8):348–9.CrossRef Scott D, Weeks D, Melchers K, Sachs G. UreI-mediated urea transport in Helicobacter pylori: an open and shut case? Trends Microbiol. 2000;8(8):348–9.CrossRef
30.
go back to reference Bury-Mone S, Skouloubris S, Labigne A, De Reuse H. The Helicobacter pylori UreI protein: role in adaptation to acidity and identification of residues essential for its activity and for acid activation. Mol Microbiol. 2001;42(4):1021–34.CrossRef Bury-Mone S, Skouloubris S, Labigne A, De Reuse H. The Helicobacter pylori UreI protein: role in adaptation to acidity and identification of residues essential for its activity and for acid activation. Mol Microbiol. 2001;42(4):1021–34.CrossRef
31.
go back to reference Kavermann H, Burns BP, Angermuller K, Odenbreit S, Fischer W, Melchers K, Haas R. Identification and characterization of Helicobacter pylori genes essential for gastric colonization. J Exp Med. 2003;197(7):813–22.CrossRef Kavermann H, Burns BP, Angermuller K, Odenbreit S, Fischer W, Melchers K, Haas R. Identification and characterization of Helicobacter pylori genes essential for gastric colonization. J Exp Med. 2003;197(7):813–22.CrossRef
32.
go back to reference Leduc D, Gallaud J, Stingl K, de Reuse H. Coupled amino acid deamidase-transport systems essential for Helicobacter pylori colonization. Infect Immun. 2010;78(6):2782–92.CrossRef Leduc D, Gallaud J, Stingl K, de Reuse H. Coupled amino acid deamidase-transport systems essential for Helicobacter pylori colonization. Infect Immun. 2010;78(6):2782–92.CrossRef
33.
go back to reference Weinberg MV, Maier RJ. Peptide transport in Helicobacter pylori: roles of dpp and opp systems and evidence for additional peptide transporters. J Bacteriol. 2007;189(9):3392–402.CrossRef Weinberg MV, Maier RJ. Peptide transport in Helicobacter pylori: roles of dpp and opp systems and evidence for additional peptide transporters. J Bacteriol. 2007;189(9):3392–402.CrossRef
34.
go back to reference Huang JY, Goers Sweeney E, Guillemin K, Amieva MR. Multiple acid sensors control Helicobacter pylori colonization of the stomach. PLoS Pathog. 2017;13(1):e1006118.CrossRef Huang JY, Goers Sweeney E, Guillemin K, Amieva MR. Multiple acid sensors control Helicobacter pylori colonization of the stomach. PLoS Pathog. 2017;13(1):e1006118.CrossRef
35.
go back to reference Huang JY, Sweeney EG, Sigal M, Zhang HC, Remington SJ, Cantrell MA, Kuo CJ, Guillemin K, Amieva MR. Chemodetection and destruction of host urea allows Helicobacter pylori to locate the epithelium. Cell Host Microbe. 2015;18(2):147–56.CrossRef Huang JY, Sweeney EG, Sigal M, Zhang HC, Remington SJ, Cantrell MA, Kuo CJ, Guillemin K, Amieva MR. Chemodetection and destruction of host urea allows Helicobacter pylori to locate the epithelium. Cell Host Microbe. 2015;18(2):147–56.CrossRef
36.
go back to reference Williams SM, Chen YT, Andermann TM, Carter JE, McGee DJ, Ottemann KM. Helicobacter pylori chemotaxis modulates inflammation and bacterium-gastric epithelium interactions in infected mice. Infect Immun. 2007;75(8):3747–57.CrossRef Williams SM, Chen YT, Andermann TM, Carter JE, McGee DJ, Ottemann KM. Helicobacter pylori chemotaxis modulates inflammation and bacterium-gastric epithelium interactions in infected mice. Infect Immun. 2007;75(8):3747–57.CrossRef
37.
go back to reference McGee DJ, Langford ML, Watson EL, Carter JE, Chen YT, Ottemann KM. Colonization and inflammation deficiencies in Mongolian gerbils infected by Helicobacter pylori chemotaxis mutants. Infect Immun. 2005;73(3):1820–7.CrossRef McGee DJ, Langford ML, Watson EL, Carter JE, Chen YT, Ottemann KM. Colonization and inflammation deficiencies in Mongolian gerbils infected by Helicobacter pylori chemotaxis mutants. Infect Immun. 2005;73(3):1820–7.CrossRef
38.
go back to reference Pernitzsch SR, Tirier SM, Beier D, Sharma CM. A variable homopolymeric G-repeat defines small RNA-mediated posttranscriptional regulation of a chemotaxis receptor in Helicobacter pylori. Proc Natl Acad Sci USA. 2014;111(4):E501–510.CrossRef Pernitzsch SR, Tirier SM, Beier D, Sharma CM. A variable homopolymeric G-repeat defines small RNA-mediated posttranscriptional regulation of a chemotaxis receptor in Helicobacter pylori. Proc Natl Acad Sci USA. 2014;111(4):E501–510.CrossRef
39.
go back to reference Strugatsky D, McNulty R, Munson K, Chen CK, Soltis SM, Sachs G, Luecke H. Structure of the proton-gated urea channel from the gastric pathogen Helicobacter pylori. Nature. 2013;493(7431):255–8.CrossRef Strugatsky D, McNulty R, Munson K, Chen CK, Soltis SM, Sachs G, Luecke H. Structure of the proton-gated urea channel from the gastric pathogen Helicobacter pylori. Nature. 2013;493(7431):255–8.CrossRef
40.
go back to reference Savvides SN, Yeo HJ, Beck MR, Blaesing F, Lurz R, Lanka E, Buhrdorf R, Fischer W, Haas R, Waksman G. VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 2003;22(9):1969–80.CrossRef Savvides SN, Yeo HJ, Beck MR, Blaesing F, Lurz R, Lanka E, Buhrdorf R, Fischer W, Haas R, Waksman G. VirB11 ATPases are dynamic hexameric assemblies: new insights into bacterial type IV secretion. EMBO J. 2003;22(9):1969–80.CrossRef
41.
go back to reference Weeks DL, Sachs G. Sites of pH regulation of the urea channel of Helicobacter pylori. Mol Microbiol. 2001;40(6):1249–59.CrossRef Weeks DL, Sachs G. Sites of pH regulation of the urea channel of Helicobacter pylori. Mol Microbiol. 2001;40(6):1249–59.CrossRef
42.
go back to reference Goers Sweeney E, Henderson JN, Goers J, Wreden C, Hicks KG, Foster JK, Parthasarathy R, Remington SJ, Guillemin K. Structure and proposed mechanism for the pH-sensing Helicobacter pylori chemoreceptor TlpB. Structure. 2012;20(7):1177–88.CrossRef Goers Sweeney E, Henderson JN, Goers J, Wreden C, Hicks KG, Foster JK, Parthasarathy R, Remington SJ, Guillemin K. Structure and proposed mechanism for the pH-sensing Helicobacter pylori chemoreceptor TlpB. Structure. 2012;20(7):1177–88.CrossRef
Metadata
Title
Genome-wide mutation analysis of Helicobacter pylori after inoculation to Mongolian gerbils
Authors
Rumiko Suzuki
Kazuhito Satou
Akino Shiroma
Makiko Shimoji
Kuniko Teruya
Takashi Matsumoto
Junko Akada
Takashi Hirano
Yoshio Yamaoka
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2019
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-019-0326-5

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