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.
Donnenberg
M S
MS
Center for Vaccine Development, University of Maryland, Baltimore 21201.
Tacket
C O
CO
James
S P
SP
Losonsky
G
G
Nataro
J P
JP
Wasserman
S S
SS
Kaper
J B
JB
Levine
M M
MM
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