A unique Helicobacter pylori strain to study gastric cancer development
ABSTRACT Helicobacter pylori colonizes a majority of the human population worldwide and can trigger development of a variety of gastric diseases. Since the bacterium is classified as a carcinogen, elucidation of the characteristics of H. pylori that influence gastric carcinogenesis is a high priorit...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2025-01-01
|
| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02163-24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841556100219928576 |
|---|---|
| author | Jeannette M. Whitmire Ian H. Windham Morris O. Makobongo Mandy D. Westland Sirena C. Tran Jaume Piñol Yvonne Hui Rasha Raheem Alkarkoushi Oscar Q. Pich David J. McGee M. Blanca Piazuelo Angela Melton-Celsa Traci L. Testerman Timothy L. Cover D. Scott Merrell |
| author_facet | Jeannette M. Whitmire Ian H. Windham Morris O. Makobongo Mandy D. Westland Sirena C. Tran Jaume Piñol Yvonne Hui Rasha Raheem Alkarkoushi Oscar Q. Pich David J. McGee M. Blanca Piazuelo Angela Melton-Celsa Traci L. Testerman Timothy L. Cover D. Scott Merrell |
| author_sort | Jeannette M. Whitmire |
| collection | DOAJ |
| description | ABSTRACT Helicobacter pylori colonizes a majority of the human population worldwide and can trigger development of a variety of gastric diseases. Since the bacterium is classified as a carcinogen, elucidation of the characteristics of H. pylori that influence gastric carcinogenesis is a high priority. To this end, the Mongolian gerbil infection model has proven to be an important tool to study gastric cancer progression. However, only a small number of H. pylori strains have been evaluated in the gerbil model. Thus, to identify additional strains able to colonize and induce disease in this model, several H. pylori strains were used to infect Mongolian gerbils, and stomachs were harvested at multiple timepoints to assess colonization and gastric pathology. The USU101 strain reproducibly colonized Mongolian gerbils and induced gastric inflammation in the majority of the animals 1 month after infection. Adenocarcinoma or dysplasia was observed in the majority of gerbils by 2 months post-infection. To define the contribution of key virulence factors to this process, isogenic strains lacking cagA or vacA, along with restorant strains containing a wild-type (WT) copy of the genes, were studied. The ΔcagA USU101 strain colonized gerbils at levels similar to WT, but did not induce comparable levels of inflammation or disease. In contrast, the ΔvacA USU101 strain did not colonize gerbils, and the stomach pathology resembled that of the mock-infected animals. The restorant USU101 strains expressed the CagA and VacA proteins in vitro, and in vivo experiments with Mongolian gerbils showed a restoration of colonization levels and inflammation scores comparable to those observed in WT USU101. Our studies indicate that the USU101 strain is a valuable tool to study H. pylori-induced disease.IMPORTANCEGastric cancer is the fifth leading cause of cancer-related death globally; the majority of gastric cancers are associated with Helicobacter pylori infection. Infection of Mongolian gerbils with H. pylori has been shown to result in induction of gastric cancer, but few H. pylori strains have been studied in this model; this limits our ability to fully understand gastric cancer pathogenesis in humans because H. pylori strains are notoriously heterogenous. Our studies reveal that USU101 represents a unique H. pylori strain that can be added to our repertoire of strains to study gastric cancer development in the Mongolian gerbil model. |
| format | Article |
| id | doaj-art-7fbea3b6a5724a7b96806c43c9970c31 |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-7fbea3b6a5724a7b96806c43c9970c312025-01-07T14:05:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-01-0113110.1128/spectrum.02163-24A unique Helicobacter pylori strain to study gastric cancer developmentJeannette M. Whitmire0Ian H. Windham1Morris O. Makobongo2Mandy D. Westland3Sirena C. Tran4Jaume Piñol5Yvonne Hui6Rasha Raheem Alkarkoushi7Oscar Q. Pich8David J. McGee9M. Blanca Piazuelo10Angela Melton-Celsa11Traci L. Testerman12Timothy L. Cover13D. Scott Merrell14Uniformed Services University of the Health Sciences, Bethesda, Maryland, USAUniformed Services University of the Health Sciences, Bethesda, Maryland, USAUniformed Services University of the Health Sciences, Bethesda, Maryland, USAVanderbilt University, Nashville, Tennessee, USAVanderbilt University, Nashville, Tennessee, USAInstitut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, SpainUniversity of South Carolina School of Medicine, Columbia, South Carolina, USAUniversity of South Carolina School of Medicine, Columbia, South Carolina, USAInstitut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, SpainDepartment of Microbiology and Immunology, LSU Health Sciences Center-Shreveport, Shreveport, Louisiana, USAVanderbilt University Medical Center, Nashville, Tennessee, USAUniformed Services University of the Health Sciences, Bethesda, Maryland, USAUniversity of South Carolina School of Medicine, Columbia, South Carolina, USAVanderbilt University, Nashville, Tennessee, USAUniformed Services University of the Health Sciences, Bethesda, Maryland, USAABSTRACT Helicobacter pylori colonizes a majority of the human population worldwide and can trigger development of a variety of gastric diseases. Since the bacterium is classified as a carcinogen, elucidation of the characteristics of H. pylori that influence gastric carcinogenesis is a high priority. To this end, the Mongolian gerbil infection model has proven to be an important tool to study gastric cancer progression. However, only a small number of H. pylori strains have been evaluated in the gerbil model. Thus, to identify additional strains able to colonize and induce disease in this model, several H. pylori strains were used to infect Mongolian gerbils, and stomachs were harvested at multiple timepoints to assess colonization and gastric pathology. The USU101 strain reproducibly colonized Mongolian gerbils and induced gastric inflammation in the majority of the animals 1 month after infection. Adenocarcinoma or dysplasia was observed in the majority of gerbils by 2 months post-infection. To define the contribution of key virulence factors to this process, isogenic strains lacking cagA or vacA, along with restorant strains containing a wild-type (WT) copy of the genes, were studied. The ΔcagA USU101 strain colonized gerbils at levels similar to WT, but did not induce comparable levels of inflammation or disease. In contrast, the ΔvacA USU101 strain did not colonize gerbils, and the stomach pathology resembled that of the mock-infected animals. The restorant USU101 strains expressed the CagA and VacA proteins in vitro, and in vivo experiments with Mongolian gerbils showed a restoration of colonization levels and inflammation scores comparable to those observed in WT USU101. Our studies indicate that the USU101 strain is a valuable tool to study H. pylori-induced disease.IMPORTANCEGastric cancer is the fifth leading cause of cancer-related death globally; the majority of gastric cancers are associated with Helicobacter pylori infection. Infection of Mongolian gerbils with H. pylori has been shown to result in induction of gastric cancer, but few H. pylori strains have been studied in this model; this limits our ability to fully understand gastric cancer pathogenesis in humans because H. pylori strains are notoriously heterogenous. Our studies reveal that USU101 represents a unique H. pylori strain that can be added to our repertoire of strains to study gastric cancer development in the Mongolian gerbil model.https://journals.asm.org/doi/10.1128/spectrum.02163-24H. pyloriMongolian gerbilsgastric adenocarcinomaCagAVacA |
| spellingShingle | Jeannette M. Whitmire Ian H. Windham Morris O. Makobongo Mandy D. Westland Sirena C. Tran Jaume Piñol Yvonne Hui Rasha Raheem Alkarkoushi Oscar Q. Pich David J. McGee M. Blanca Piazuelo Angela Melton-Celsa Traci L. Testerman Timothy L. Cover D. Scott Merrell A unique Helicobacter pylori strain to study gastric cancer development Microbiology Spectrum H. pylori Mongolian gerbils gastric adenocarcinoma CagA VacA |
| title | A unique Helicobacter pylori strain to study gastric cancer development |
| title_full | A unique Helicobacter pylori strain to study gastric cancer development |
| title_fullStr | A unique Helicobacter pylori strain to study gastric cancer development |
| title_full_unstemmed | A unique Helicobacter pylori strain to study gastric cancer development |
| title_short | A unique Helicobacter pylori strain to study gastric cancer development |
| title_sort | unique helicobacter pylori strain to study gastric cancer development |
| topic | H. pylori Mongolian gerbils gastric adenocarcinoma CagA VacA |
| url | https://journals.asm.org/doi/10.1128/spectrum.02163-24 |
| work_keys_str_mv | AT jeannettemwhitmire auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT ianhwindham auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT morrisomakobongo auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT mandydwestland auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT sirenactran auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT jaumepinol auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT yvonnehui auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT rasharaheemalkarkoushi auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT oscarqpich auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT davidjmcgee auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT mblancapiazuelo auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT angelameltoncelsa auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT traciltesterman auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT timothylcover auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT dscottmerrell auniquehelicobacterpyloristraintostudygastriccancerdevelopment AT jeannettemwhitmire uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT ianhwindham uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT morrisomakobongo uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT mandydwestland uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT sirenactran uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT jaumepinol uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT yvonnehui uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT rasharaheemalkarkoushi uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT oscarqpich uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT davidjmcgee uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT mblancapiazuelo uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT angelameltoncelsa uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT traciltesterman uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT timothylcover uniquehelicobacterpyloristraintostudygastriccancerdevelopment AT dscottmerrell uniquehelicobacterpyloristraintostudygastriccancerdevelopment |