Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium.

Ghaem-Maghami, M; Simmons, C; Daniell, S; Pizza, M; Lewis, D; Frankel, G; Dougan, G

Journal article

Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium.

Abstract:: 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.

Publication status:: Published

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APA Style

Ghaem-Maghami, M., Simmons, C., Daniell, S., Pizza, M., Lewis, D., Frankel, G., & Dougan, G. (2001). Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium. Infection and Immunity, 69(9), 5597–5605.

MLA Style

Ghaem-Maghami, M., et al. “Intimin-Specific Immune Responses Prevent Bacterial Colonization by the Attaching-Effacing Pathogen Citrobacter Rodentium.” Infection and Immunity, vol. 69, no. 9, 2001, pp. 5597–605.

Chicago Style

Ghaem-Maghami, M, C Simmons, S Daniell, M Pizza, D Lewis, G Frankel, and G Dougan. 2001. “Intimin-Specific Immune Responses Prevent Bacterial Colonization by the Attaching-Effacing Pathogen Citrobacter Rodentium.” Infection and Immunity 69 (9): 5597–5605.
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