Bacterial Toxin Interaction with the Developing Intestine

An important approach to the major health problem of bacterial infection in young children has been to examine bacterial toxin binding to microvillus membrane receptors, the signal transduction produced by that interaction and the mechanisms of fluid secretion in the developing intestine as a basis for toxigenic diarrhea in the infant population. These studies indicate that receptor binding and effector responses may be subjected to developmental regulation. This regulation process of toxin interaction with the developing intestine may have an enhanced or harmful effect or, under some circumstances, may have a beneficial effect and be protective to the vulnerable child. Specific mechanisms for the developmental control of receptor expression may involve the regulation of individual glycosyltransferases responsible for the addition of receptor sugar sequences to glycolipids and/or glycoproteins, presumably at the transcriptional level. Furthermore, although highly speculative at this point, the differential expression of signal transducers (e.g., guanine nucleotide-regulatory proteins or G proteins) and ion transporters (e.g., Na+,K(+)-stimulated adenosine triphosphatase, the Cl- channels, etc.) during development may also alter the neonatal host's responsiveness. Therefore, the developmental control of microvillus membrane receptors, signal transduction mechanisms, and ion transport systems in the gastro-intestinal tract may in part contribute to the altered host sensitivity in toxigenic diarrhea of infancy.