Colonization and inflammation deficiencies in Mongolian gerbils infected by Helicobacter pylori chemotaxis mutants.
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.
McGee
David J
DJ
Department of Microbiology & Immunology, University of South Alabama College of Medicine, 307 N. University Blvd., Mobile, AL 36688, USA. dmcgee@jaguar1.usouthal.edu
Langford
Melanie L
ML
Watson
Emily L
EL
Carter
J Elliot
JE
Chen
Yu-Ting
YT
Ottemann
Karen M
KM
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
D001426:Bacterial Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins
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