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...

Descrizione completa

Salvato in:
Dettagli Bibliografici
Autore principale: Simmons, Cameron
Natura: Journal Article
Lingua:inglese
Pubblicazione: 2018
Accesso online:https://demo7.dspace.org/handle/123456789/110
Tags: Aggiungi Tag
Nessun Tag, puoi essere il primo ad aggiungerne!!
_version_ 1860822453935144960
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