Salmonella enterica Infection: Salmonellosis

Salmonella, a member of the Enterobacteriaceae, contin­ues to evoke unresolved debate over nomenclature. Among 2,500 serovars, DNA-DNA hybridization sug­gests that most serovars probably represent a single species, with the exception of Salmonella bongori.

Epizootiology and Pathogenesis

Salmonella enterica serovars Enteritidis and Typhimu- rium are the most commonly identified natural serovars in mice, and S. enterica serovar Typhimurium is a com­monly used experimental serovar. Infection is initiated by ingestion of contaminated feed or bedding, although conjunctival inoculation requires fewer organisms to establish an infection. Salmonellae exist intracellularly, stimulate their own uptake by enterocytes, and continue to survive and replicate in macrophages. Host suscepti­bility or resistance depends on a variety of factors, including age (weanlings are more susceptible than adult mice), gut microflora, strain of mice, virulence and dose of organism, route of inoculation, intercurrent infec­tions, and manipulations that impair the immune response.

Following exposure by ingestion, the incubation period is usually 3-6 days. Organisms gain entry to mucosa via fimbrial attachment to M cells, followed by uptake through type III secretion systems that induce phagocytosis by enterocytes, and modification of the intracellular environment of macrophages to allow sur­vival. Initial replication in enterocytes is followed by multiplication in gut-associated lymphoid tissue and then spread to the systemic circulation. In a small per­centage of animals, there may be intermittent shedding of the organism in the feces for several months. The organism may also be harbored in the upper respiratory tract in carrier mice. Salmonella is readily killed by neu­trophils, and neutrophil function is an important factor in resistance, but the bacterium has adapted to grow within macrophages, effectively evading clearance. In the liver, bacteria replicate intracellularly within macro­phages, producing focal histiocytic granulomata as the hallmark lesion. Genetically susceptible mice die from massive bacterial proliferation and tissue destruction related to endotoxin.

Pathology

Clinical illness among naturally infected mice is rare, and persistently infected carrier mice are common. Clin­ical signs, when present, include diarrhea, anorexia, weight loss, conjunctivitis, and variable mortality.

Diagnosis

Isolation and identification of the organism from sites such as liver, spleen, mesenteric lymph nodes, and intestine are essential and must accompany the standard macroscopic and histopathologic findings. Culture requires enrichment with Selenite F broth plus cysteine, followed by streaking on brilliant green agar. When screening a colony for possible Salmonella carriers, cul­turing of individual fecal samples is more sensitive than using pooled samples, and the highest rate of detection

FIG. 1.63. Liver from a mouse with salmonellosis. The circumscribed lesion consists of aggregations of histiocytes.

among carriers is achieved by culturing mesenteric lymph node, since fecal shedding is intermittent. Differ­ential diagnoses include Tyzzer's disease, coronaviral hepatitis, mousepox, Helicobacter hepatitis, and pseudo- moniasis. Spontaneous mesenteric lymphadenopathy (mesenteric disease) can also occur in aging mice.