Role of the eaeA gene in experimental enteropathogenic Escherichia coli infection.
Enteropathogenic Escherichia coli (EPEC) infections are a leading cause of infant diarrhea in developing countries. Recently eaeA, a gene necessary for the characteristic intimate attachment of EPEC to epithelial cells in tissue culture, was described. We conducted a randomized, double-blind study to determine the role of the eaeA gene in human EPEC infection. 11 adult volunteers ingested 2 x 10(10) colony-forming units of O127:H6 EPEC strain E2348/69, and an equal number received the same dose of an isogenic eaeA deletion mutant constructed from E2348/69. Volunteers were monitored for the development of diarrhea, fever, and systemic and gastrointestinal complaints. Diarrhea developed in all 11 volunteers who received E2348/69 and in 4 of 11 who received the mutant (P = 0.002). Fever was more common in recipients of the wild-type strain (P = 0.024). Stool volumes were lower in recipients of the mutant. All volunteers seroconverted to E2348/69 LPS, but the geometric mean peak titers of serum IgG and IgA in recipients of the mutant were lower than those of recipients of the wild-type strain. IgA against LPS was detected in the jejunal fluid of six of six recipients of E2348/69 and 5/6 recipients of the mutant. This study unambiguously assigns a role for eaeA as an EPEC virulence gene, but the residual diarrhea seen in recipients of the mutant indicates that other factors are involved.
Center for Vaccine Development, University of Maryland, Baltimore 21201.
M S
MS
Donnenberg
C O
CO
Tacket
S P
SP
James
G
G
Losonsky
J P
JP
Nataro
S S
SS
Wasserman
J B
JB
Kaper
M M
MM
Levine
D018829:Adhesins, Bacterial; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D003967:Diarrhea / Q000382:microbiology*; D004311:Double-Blind Method; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology*; D029968:Escherichia coli Proteins; D005798:Genes, Bacterial; D006801:Humans; D017384:Sequence Deletion
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C073819:eaeA protein, E coli