Experimental Salmonellosis

Mice were infected with smooth or rough strains of Salmonella enteritidis and Salmonella typhimurium and viable bacterial cells found in the liver of the inoculated animals were enumerated by plating homogenates of tissues on nutrient agar plates containing 0.35 M sucrose. Some rough strains of these Salmonella were recovered in the bacteria seen on these plates and appeared able to form colonies only on the sucrose-containing medium but not on an identical medium without added sucrose. This population did not appear in the liver of animals until at least 24 hr after infection. The number of bacteria capable of forming colonies only on the hypertonic medium was found to vary with the time after infection and the strain of bacteria used for infection. From the results of morphological examination of cells of the colonies developing on the hypertonic plates, these bacterial forms were thought to result from unstable L forms in the infected tissues. Possible processes of the formation of these L forms in vivo and their significance in induction of anti-infectious immunity are discussed.     

Porcine Salmonellosis

Renal vascular lesions associated with experimentally induced septicemic porcine salmonellosis consisted of fibrinoid necrosis of the vessel walls and fibrin thrombi within the lumina of interlobular arteries, afferent arterioles and glomerular capillary loops. Extrarenal vascular alterations were predominantly localized to the skin and the lungs. In these sites, too, mere fibrin thrombi were found in the capillaries, whereas mixed thrombi, consisting of fibrin, platelets, leucocytes and erythrocytes were present in larger vessels. The conclusion is drawn that the renal vascular injury is completely compatible to the generalized Shwartzman reaction, while the extrarenal vascular changes may only in part depend on this mechanism.     

Experimental Salmonellosis

When mononuclear phagocytes (macrophages), were infected with Salmonella enteritidis and confined in a diffusion chamber to incubate with normal macrophages, they confer on the normal macrophages cellular immunity, as detected by inhibition to intracellular multiplication of a virulent strain 116-54 and resistance to cellular degeneration caused by phagocytosis of bacteria. An immune ribonucleic acid (RNA) was extracted from the peritoneal macrophages maintained in tissue culture bottles in a homogeneous cell population which had been infected with strains of 5. enteritidis. When peritoneal macrophages, cultured in a homogeneous cell population, were treated in vitro with this agent, they developed cellular immunity and cellular antibody. The RNA preparation was not inactived by treatment with deoxyribonuclease, with pronase or with antibodies to a virulent strain 116-54 of S. enteritidis. These facts suggest that the macrophages constitute a cell line responsible for active antibody formation.     

Experimental Salmonellosis

An immune ribonucleic acid (RNA) preparation was obtained from the spleens of mice immunized with a live vaccine of Salmonella enteritidis. When peritoneal macrophages were infected with S. enteritidis 116–54 which had been treated by mixed cultivation with the peritoneal exudate cells of mice previously treated with an immune RNA preparation, they showed cellular resistance against the infecting bacteria. According to the results described previously and those described in this article, it can be concluded that the cellular resistance against an infection with S. enteritidis is traceable to a cellular antibody (or antibodies) detected in macrophages of mice immunized with a live vaccine of the same organism or of mice treated in vivo (or in vitro) with an immune RNA preparation.     

Mechanistic Modeling of Salmonellosis

The serious limitation of the available human data contributes to the need for making simplifying assumptions for dose-response modeling which has led to frequent use of a single function, the beta-Poisson function, as a default dose-response model form. This function is a concave, low-dose linear function. Sub-linear or convex curves may be more appropriate for some host-pathogen interactions due to the series of highly regulated innate and acquired defense systems of the healthy human body that protect against most microbial challenges. A systematic investigation of the steps of non-typhoid salmonellosis in humans leads to biological motivations for sub-linear, or non-concave, dose-response curves in microbial risk assessment. Three phenomena were identified that might contribute to sub-linear, or non-concave, dose-response curves: (1) clumping of bacterial cells in microcolonies in a food matrix; (2) quorum sensing, or density-dependency in expression of virulence genes or other metabolic actions; and (3) need, at least in some circumstances, for multiple lesions for progression to symptomatic illness. This investigation suggests that microbial risk assessors should routinely employ a variety of model forms in addition to the commonly used beta-Poisson model to depict more fully the uncertainty of the true dose-response model.     

Salmonellosis in white-tailed deer fawns

Experimental infection of white-tailed deer fawns with Salmonella meleagridis was accomplished. The fawns suffered clinical illness, similar to spontaneous cases observed in the field. This disease may be an important factor in fawn survival in wild herds based on the frequency with which Salmonellae could be isolated in wild fawns. The clinical disease was acute, characterized by rapid depression and dehydration. Death ensued in three of eight experimental cases. The survivors suffered clinical illness.