title: Colonization and inflammation deficiencies in Mongolian gerbils infected by Helicobacter pylori chemotaxis mutants.
abstract: Helicobacter pylori causes disease in the human stomach and in mouse and gerbil stomach models. Previous results have shown that motility is critical for H. pylori to colonize mice, gerbils, and other animal models. The role of chemotaxis, however, in colonization and disease is less well understood. Two genes in the H. pylori chemotaxis pathway, cheY and tlpB, which encode the chemotaxis response regulator and a methyl-accepting chemoreceptor, respectively, were disrupted. The cheY mutation was complemented with a wild-type copy of cheY inserted into the chromosomal rdxA gene. The cheY mutant lost chemotaxis but retained motility, while all other strains were motile and chemotactic in vitro. These strains were inoculated into gerbils either alone or in combination with the wild-type strain, and colonization and inflammation were assessed. While the cheY mutant completely failed to colonize gerbil stomachs, the tlpB mutant colonized at levels similar to those of the wild type. With the tlpB mutant, there was a substantial decrease in inflammation in the gerbil stomach compared to that with the wild type. Furthermore, there were differences in the numbers of each immune cell in the tlpB-mutant-infected stomach: the ratio of lymphocytes to neutrophils was about 8 to 1 in the wild type but only about 1 to 1 in the mutant. These results suggest that the TlpB chemoreceptor plays an important role in the inflammatory response while the CheY chemotaxis regulator plays a critical role in initial colonization. Chemotaxis mutants may provide new insights into the steps involved in H. pylori pathogenesis.
authors.affiliation: Department of Microbiology & Immunology, University of South Alabama College of Medicine, 307 N. University Blvd., Mobile, AL 36688, USA. dmcgee@jaguar1.usouthal.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: McGee
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Langford
authors.forename: Emily L
authors.initials: EL
authors.lastname: Watson
authors.forename: J Elliot
authors.initials: JE
authors.lastname: Carter
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Chen
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ottemann
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000254:growth & development* / Q000276:immunology / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D009154:Mutation; D013270:Stomach / Q000276:immunology / Q000382:microbiology
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins
references.citation: Infect Immun. 2000 Apr;68(4):2016-23
references.pmid: 10722597
references.citation: Gut. 1998 Jul;43 Suppl 1:S2-5
references.pmid: 9764030
references.citation: J Bacteriol. 2000 Jul;182(14):3948-54
references.pmid: 10869072
references.citation: Mol Microbiol. 2000 Sep;37(5):1066-74
references.pmid: 10972825
references.citation: Microbes Infect. 2000 Aug;2(10):1207-14
references.pmid: 11008110
references.citation: J Exp Med. 2000 Dec 4;192(11):1601-10
references.pmid: 11104802
references.citation: Infect Immun. 2001 Feb;69(2):730-6
references.pmid: 11159961
references.citation: J Clin Invest. 2001 Mar;107(5):611-20
references.pmid: 11238562
references.citation: Nat Rev Mol Cell Biol. 2001 Jun;2(6):457-66
references.pmid: 11389469
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6889-94
references.pmid: 11391007
references.citation: Microbiology. 2001 Sep;147(Pt 9):2493-504
references.pmid: 11535789
references.citation: Infect Immun. 2002 Feb;70(2):685-91
references.pmid: 11796600
references.citation: J Infect Dis. 2002 Feb 1;185(3):341-7
references.pmid: 11807716
references.citation: Infect Immun. 2002 Apr;70(4):1984-90
references.pmid: 11895962
references.citation: Helicobacter. 2002 Apr;7(2):139-40; author reply 140-1
references.pmid: 11966874
references.citation: Int J Med Microbiol. 2002 Mar;291(8):605-14
references.pmid: 12008914
references.citation: Aliment Pharmacol Ther. 2002 Jul;16(7):1249-59
references.pmid: 12144574
references.citation: J Pathol. 2004 Feb;202(2):197-207
references.pmid: 14743502
references.citation: J Med Microbiol. 1992 Aug;37(2):123-7
references.pmid: 1629897
references.citation: J Bacteriol. 1994 May;176(9):2736-9
references.pmid: 8169224
references.citation: Vet Pathol. 1995 Sep;32(5):489-97
references.pmid: 8578639
references.citation: Annu Rev Microbiol. 1995;49:489-522
references.pmid: 8561469
references.citation: Cancer Res. 1998 Oct 1;58(19):4255-9
references.pmid: 9766647
references.citation: Nature. 1999 Jan 14;397(6715):176-80
references.pmid: 9923682
references.citation: J Immunol. 1999 Aug 1;163(3):1490-7
references.pmid: 10415051
references.citation: Adv Microb Physiol. 1999;41:229-89
references.pmid: 10500847
references.citation: Infect Immun. 2005 Feb;73(2):803-11
references.pmid: 15664919
references.citation: Infect Immun. 2002 Oct;70(10):5877-81
references.pmid: 12228322
references.citation: J Med Microbiol. 2002 Nov;51(11):958-70
references.pmid: 12448680
references.citation: J Exp Med. 2003 Apr 7;197(7):813-22
references.pmid: 12668646
references.citation: FEMS Microbiol Lett. 2003 Jul 29;224(2):175-81
references.pmid: 12892880
references.citation: Helicobacter. 2003;8 Suppl 1:31-5
references.pmid: 14617215
references.citation: Infect Immun. 1996 Jul;64(7):2445-8
references.pmid: 8698465
references.citation: Gastroenterology. 1997 Apr;112(4):1386-97
references.pmid: 9098027
references.citation: Mol Microbiol. 1997 Jun;24(6):1109-17
references.pmid: 9218761
references.citation: Infect Immun. 1997 Aug;65(8):3310-6
references.pmid: 9234792
references.citation: J Bacteriol. 1997 Aug;179(15):4676-83
references.pmid: 9244252
references.citation: Nature. 1997 Aug 7;388(6642):539-47
references.pmid: 9252185
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3925-30
references.pmid: 9520469
references.citation: Infect Immun. 1998 Oct;66(10):4856-66
references.pmid: 9746590
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7533-8
references.pmid: 10852959