Infant botulism is the age-related illnes caused by toxin produced by C. botulinum infecting the gut; in a fulminant form, it may be one cause of sudden infant (crib) death syndrome. The infectious process can be duplicated in conventional infant mice and in adult mice whose intestinal flora has been altered with antimicrobial agents, but these experimental infections are not accompanied by overt illness. Botulism is induced by intracolonically injecting saline (enema) to nonsytmptomatically infected mice. Holding the nonsymptomatically infected mice at 37DegreeC may have a similar effect as an enema. The possibility will be confirmed and the stress timing eliciting severest illness will be determined. Combining temperature stress with enema may induce a severer response than either treatment by itself. Results may lead to better understanding of conditions in which infant botulism is rapidly fatal. The often long but uneventful convalescences of clinical cases while toxin production continues may be due to activation during early infection stage of system forming secretory IgA that neutralized botulinum toxin. The possibility can be studied by titrating antibotulinum toxin IgA in the gut at different periods of chronic monoassociation of mice by C. botulinum. Gnotobiotic mice, resulting from feeding different combinations of pure cultures of different organisms, will be tested for resistance to C. botulinum infection. Organisms will include Clostridium sporogenes and putrefactive anaerobe 3679, both closely related to the challenge inoculum. This kind of study is to see if natural resistance has several independently active barrier systems. Floras preventing intestinal C. botulinum infection will be tested for ability to displace an established C. botulinum infection. When monoassociating the mouse cecum and colon, the pathogen is intimately associated with the mucous gel but does not bind to the epithelium of the gut. If apparent affinity between pathogen and mucous gel is due to ability of organism to utilize mucous for its growth, hexose and/or protein in mucous from monoassociated gut should be lower than in mucous from germfree mice. If not, the pathogen may be able to bind radiolabeled mucous. Objectives of this study phase is to determine better the intestinal habitat of the pathogen.
