Mechanisms of Adherence of Escherichia coli to Enterocytes: Their Possible Role in Intractable Infant Diarrhea*

Although the classical definition of intractable diarrhea of infancy (1), which includes three or more stools negative for bacterial pathogens, would tend to exclude a role for enteric infection in the pathogenesis of this form of diarrheal disease, a role for pathogenic E. coli may remain. The decade or more since this definition was proposed has seen tremendous advances in the laboratory recognition of pathogenic properties of Escherichia coli strains but no parallel advance in bringing these laboratory tests into clinical use. The fact remains that in most clinical laboratories, particularly those in developing countries, methods are not currently available to identify pathogenic E. coli in specific cases of diarrheal diseases. More often, tests for enterotoxin production, colonization factor antigens, and invasiveness of E. coli, or for the genes encoding for these properties, are only available in research laboratories or in centers performing epidemiological studies. The results are not often readily available to clinicians caring for sick children. At the same time, screening E. coli strains for enteropathic serotypes has fallen into disuse because of a general feeling, unfortunately promoted by influential health organizations, that serotyping was unlikely to remain of clinical relevance with the development of more sophisticated laboratory tests reflecting more specific knowledge of pathogenic mechanisms. In part, serotyping has also fallen into disuse because of a real difficulty in identifying complete serotypes (including O, H, and K antigens) outside of the reference laboratory. Thus, at this time, even in the absence of positive stools for pathogens, E. coli should not be ignored, since they may yet emerge as having a significant role in this symptom complex. Of particular interest in this context are mechanisms of adherence and colonization whereby Escherichia coli can establish themselves as more or less permanent residents at the mucosal surface (Fig. 1). Three types of pathological