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 ⌬espB 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 ⌬espB 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 ⌬espB 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.Enteropathogenic Escherichia coli (EPEC) strains cause serious diarrhea among infants in developing countries throughout the world (4). Because EPEC strains isolated from humans do not cause diarrhea in animals, EPEC pathogenicity and the role of EPEC virulence factors in disease can only be tested in volunteer studies (2,5,20,21). During human infections, typical EPEC strains display two phenotypes, localized adherence and the attaching-and-effacing effect, which are reproduced in tissue culture. Localized adherence is dependent upon a type IV fimbria known as the bundle-forming pilus, which is encoded by a cluster of fourteen genes on a large plasmid common to EPEC strains (28, 30). The attaching-and-effacing effect is characterized by profound changes in the architecture of the host cell, with loss of microvilli and accumulations of cytoskeletal proteins within a cup-like pedestal upon which the bacteria rest (17,18
Our study demonstrates that H. pylori infection is significantly less prevalent in patients with reflux esophagitis and may protect against its development. In duodenal ulcer patients, this effect was more dramatic. Further study is required to confirm these findings and elucidate mechanisms underlying possible beneficial effects of H. pylori.
Laparoscopic Nissen fundoplication is effective in relieving the symptoms of laryngopharyngeal reflux in a carefully selected patient population. Benefits are seen within 1 month of surgery and persist for at least 3 years.
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