Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium
The formation of attaching and effacing (A/E) lesions on gut enterocytes is central to the pathogenesis of enterohemorrhagic (EHEC) Escherichia coli, enteropathogenic E. coli (EPEC), and the rodent pathogen Citrobacter rodentium. Genes encoding A/E lesion formation map to a chromosomal pathogenicity...
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| Natura: | Journal Article |
| Lingua: | inglese |
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2018
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| Accesso online: | https://demo7.dspace.org/handle/123456789/110 |
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| _version_ | 1860822453935144960 |
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| author | Simmons, Cameron |
| author_browse | Simmons, Cameron |
| author_facet | Simmons, Cameron |
| author_sort | Simmons, Cameron |
| collection | DSpace |
| description | The formation of attaching and effacing (A/E) lesions on gut enterocytes is central to the pathogenesis of enterohemorrhagic (EHEC) Escherichia coli, enteropathogenic E. coli (EPEC), and the rodent pathogen Citrobacter rodentium. Genes encoding A/E lesion formation map to a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Here we show that the LEE-encoded proteins EspA, EspB, Tir, and intimin are the targets of long-lived humoral immune responses in C. rodentium-infected mice. Mice infected with C. rodentium developed robust acquired immunity and were resistant to reinfection with wild-type C. rodentium or a C. rodentium derivative, DBS255(pCVD438), which expressed intimin derived from EPEC strain E2348/69. The receptor-binding domain of intimin polypeptides is located within the carboxy-terminal 280 amino acids (Int280). Mucosal and systemic vaccination regimens using enterotoxin-based adjuvants were employed to elicit immune responses to recombinant Int280alpha from EPEC strain E2348/69. Mice vaccinated subcutaneously with Int280alpha, in the absence of adjuvant, were significantly more resistant to oral challenge with DBS255(pCVD438) but not with wild-type C. rodentium. This type-specific immunity could not be overcome by employing an exposed, highly conserved domain of intimin (Int388-667) as a vaccine. These results show that anti-intimin immune responses can modulate the outcome of a C. rodentium infection and support the use of intimin as a component of a type-specific EPEC or EHEC vaccine. |
| format | Journal Article |
| id | oai:localhost:123456789-110 |
| institution | DSPACE.FCHPT |
| language | English |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| record_format | dspace |
| spelling | oai:localhost:123456789-1102021-04-07T16:30:07Z Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium Simmons, Cameron The formation of attaching and effacing (A/E) lesions on gut enterocytes is central to the pathogenesis of enterohemorrhagic (EHEC) Escherichia coli, enteropathogenic E. coli (EPEC), and the rodent pathogen Citrobacter rodentium. Genes encoding A/E lesion formation map to a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Here we show that the LEE-encoded proteins EspA, EspB, Tir, and intimin are the targets of long-lived humoral immune responses in C. rodentium-infected mice. Mice infected with C. rodentium developed robust acquired immunity and were resistant to reinfection with wild-type C. rodentium or a C. rodentium derivative, DBS255(pCVD438), which expressed intimin derived from EPEC strain E2348/69. The receptor-binding domain of intimin polypeptides is located within the carboxy-terminal 280 amino acids (Int280). Mucosal and systemic vaccination regimens using enterotoxin-based adjuvants were employed to elicit immune responses to recombinant Int280alpha from EPEC strain E2348/69. Mice vaccinated subcutaneously with Int280alpha, in the absence of adjuvant, were significantly more resistant to oral challenge with DBS255(pCVD438) but not with wild-type C. rodentium. This type-specific immunity could not be overcome by employing an exposed, highly conserved domain of intimin (Int388-667) as a vaccine. These results show that anti-intimin immune responses can modulate the outcome of a C. rodentium infection and support the use of intimin as a component of a type-specific EPEC or EHEC vaccine. 2018-09-14T11:14:55Z 2017-07-05T05:00:49Z 2018-09-14T11:14:55Z 2001-09-01 Journal Article https://demo7.dspace.org/handle/123456789/110 English |
| spellingShingle | Simmons, Cameron Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium |
| title | Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium |
| title_full | Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium |
| title_fullStr | Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium |
| title_full_unstemmed | Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium |
| title_short | Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium |
| title_sort | intimin specific immune responses prevent bacterial colonization by the attaching effacing pathogen citrobacter rodentium |
| url | https://demo7.dspace.org/handle/123456789/110 |
| work_keys_str_mv | AT simmonscameron intiminspecificimmuneresponsespreventbacterialcolonizationbytheattachingeffacingpathogencitrobacterrodentium |