Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent

Kleanthous, Harry; Tibbitts, Timothy; Gray, Heather; Myers, Gene; Lee, Cynthia; Ermak, Thomas H.; Monath, Thomas P.

doi:10.1016/s0264-410x(01)00248-1

Cited by 27 publications

(19 citation statements)

References 29 publications

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“…Our differing results may be explained by differences between the two species of Helicobacter, timing, and vaccine efficacy. Vaccination outcomes are very dependent on the antigen preparation, dose of antigen, adjuvant, timing, and route of administration (17,21,40,45). In the long-term H. felis study, Sutton et al used intragastric immunization, which we found to be less effective than intranasal immunization in a preliminary experiment (Garhart et al, unpublished).…”

Section: Discussionmentioning

confidence: 82%

Clearance ofHelicobacter pyloriInfection and Resolution of Postimmunization Gastritis in a Kinetic Study of Prophylactically Immunized Mice

Garhart¹,

Redline²,

Nedrud³

et al. 2002

Infect Immun

124

128

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Patients infected with Helicobacter pylori mount an immune response which fails to clear the infection and may contribute to disease. Mice can be protected by immunization. To further characterize the H. pylori-mouse model, stomachs of unimmunized or intranasally immunized C57BL/6 mice were quantitatively cultured 3 days and 1, 2, 4, 8, 16, 32, and 52 weeks after challenge with H. pylori. At 3 days and 1 week after challenge, colonization was the same in the immunized and unimmunized mice. By 2 weeks after challenge, the immunized mice had a >2-log decrease in bacterial load, and at all later time points, they either were culture negative or had at least a 2-log decrease in bacterial load. Gastritis in the immunized mice peaked at 1 to 2 weeks after challenge and was characterized by a mixed inflammatory infiltrate and epithelial proliferation centered at the transition between corpus and antrum. By 52 weeks postchallenge, the gastric histology in the immunized mice was not different from that in control unchallenged mice. The unimmunized group began to show a reduction in bacterial load as early as 16 weeks after challenge, and by 52 weeks seven of eight unimmunized mice had developed gastritis and reduced bacterial loads. These results indicate that prophylactic immunization does not prevent colonization by H. pylori but enables mice to clear the infection or significantly reduce the number of colonizing bacteria. The reduction in bacterial load is associated with gastric inflammation that subsides over time.

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Section: Discussionmentioning

confidence: 82%

Clearance ofHelicobacter pyloriInfection and Resolution of Postimmunization Gastritis in a Kinetic Study of Prophylactically Immunized Mice

Garhart¹,

Redline²,

Nedrud³

et al. 2002

Infect Immun

124

128

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“…Based on the published crystal structure of H. pylori catalase, two residues are essential for catalysis as follows: the proximal Tyr-339, coordinated to the heme iron, and the distal His-56, essential for the formation of the main reaction intermediate, compound I (21,22). Therefore, two markerless chromosomal katA mutant versions, katA H56A and katA Y339A , were constructed in two H. pylori wild-type (WT) strains, strain 43504 and the mouse colonizing strain X47 (23). Complete deletion of ⌬katA mutants were also constructed in both parental strains.…”

Section: Resultsmentioning

confidence: 99%

Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress

Benoit

Maier

2016

Journal of Biological Chemistry

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Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H 2 O 2 ). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains (katA H56A and katA Y339A ) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalasedeletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H 2 O 2 -dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new nonenzymatic protective mechanism of action for the ubiquitous enzyme.Catalase was described over 100 years ago (1), and the enzyme's role clearly is to detoxify H 2 O 2 by converting it into H 2 O and O 2 . It is one of he most abundant proteins in cells, and it is present in most organisms, including in both plant and animal cells (2). It is oftentimes a highly expressed protein. For example, in the gastric pathogen Helicobacter pylori, catalase (KatA) levels are estimated to be 4 -5% of the total protein content (3), and the katA gene is one of the most highly expressed genes in H. pylori cells recovered from the human stomach (4). HOCl-mediated oxidation of six identified Met residues in H. pylori KatA leads to methionine sulfoxide formation (Met-O), 2 protein oligomerization, and loss of catalase activity (3). Most organisms, including Helicobacter, possess a peptide repair enzyme, methionine sulfoxide reductase (Msr), that reduces Met-O back to Met in certain oxidation-susceptible Msr-targeted proteins (5, 6). This Msr-mediated repair (along with added GroEL/ES) returns most of the catalase activity (3). Although the identified protein targets of repair are few among the total of all organisms, some of these repair targets are themselves stress-combating enzymes.Purified KatA and Msr enzymes were shown to physically interact (6), and this interaction resulted in Msr-mediated repair of five out of the six oxidized KatA Met residues (3). In addition, H. pylori KatA is ubiquitous, present in both the cytoplasm and in the periplasm and on the cell surface as well as...

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“…195 Post-immunisation gastritis may be transient, 195 challenge strain dependent, 196 and may or may not occur in different animal models. It has been reported in mice, 116,195 rhesus monkeys 171 and gnotobiotic piglets, 197 but not in Mongolian gerbils 198 or beagle dogs.…”

Section: Prospects For Future Vaccinesmentioning

confidence: 99%

The inflammatory and immune response to Helicobacter pylori infection

Robinson

Argent

Atherton

2007

Best Practice & Research Clinical Gastroenterology

159

149

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Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent

Cited by 27 publications

References 29 publications

Clearance ofHelicobacter pyloriInfection and Resolution of Postimmunization Gastritis in a Kinetic Study of Prophylactically Immunized Mice

Clearance ofHelicobacter pyloriInfection and Resolution of Postimmunization Gastritis in a Kinetic Study of Prophylactically Immunized Mice

Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress

The inflammatory and immune response to Helicobacter pylori infection

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