Role of EspB in experimental human enteropathogenic Escherichia coli infection.
Enteropathogenic Escherichia coli (EPEC), a leading cause of diarrhea among infants in developing countries, induces dramatic alterations in host cell architecture that depend on a type III secretion system. EspB, one of the proteins secreted and translocated to the host cytoplasm via this system, is required for numerous alterations in host cell structure and function. To determine the role of EspB in virulence, we conducted a randomized, double-blind trial comparing the ability of wild-type EPEC and an isogenic DeltaespB mutant strain to cause diarrhea in adult volunteers. Diarrhea developed in 9 of 10 volunteers who ingested the wild-type strain but in only 1 of 10 volunteers who ingested the DeltaespB mutant strain. Marked destruction of the microvillous brush border adjacent to adherent organisms was observed in a jejunal biopsy from a volunteer who ingested the wild-type strain but not from two volunteers who ingested the DeltaespB mutant strain. Humoral and cell-mediated immune responses to EPEC antigens were stronger among recipients of the wild-type strain. In addition, four of the volunteers who ingested the wild-type strain had lymphoproliferative responses to EspB. These results demonstrate that EspB is a critical virulence determinant of EPEC infections and suggest that EspB contributes to an immune response.
Tacket
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Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. ctacket@medicine.umaryland.edu
Sztein
M B
MB
Losonsky
G
G
Abe
A
A
Finlay
B B
BB
McNamara
B P
BP
Fantry
G T
GT
James
S P
SP
Nataro
J P
JP
Levine
M M
MM
Donnenberg
M S
MS
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001706:Biopsy; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology*; D004311:Double-Blind Method; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology*; D019453:Escherichia coli O157 / Q000472:pathogenicity; D029968:Escherichia coli Proteins; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D007583:Jejunum / Q000382:microbiology / Q000473:pathology; D008871:Microvilli / Q000473:pathology; D014611:Vaccination
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; C087863:EaeB protein, E coli; D029968:Escherichia coli Proteins; D007371:Interferon-gamma