Science about Pathogens

Only 1% of the inoculum survives the low pH during the passage through the stomach. The surviving bacteria then reach the small intestine, which contains bacteriacidal compounds, such as bile salts. About 80% of the bacteria that survive the passage through the stomach are passed with the faeces within 6-10 hours post-infection, About 15% remain localized in the lumen of the caecum and large intestines, and only 5% manage to penetrate the intestinal wall of the small intestine and reach the GALT (Gut associated lymphatic tissue).

An important factor that impedes colonization by salmonella serovars is the normal gut flora. Disruption in the endogenous flora by streptomycin treatment results in a 100,000 fold reduction in the 50% implantation dose. The phenomenon of the endogenous flora being able to prevent colonization by exogenous bacteria is known as bacterial interference. Some of these things are production of inhibitory substances, competition for tissue adhesion sites, and limiting resources.

Peyers patches serve as the main port of entry for Salmonella serovars.

Intestinal perforations at areas of Peyer’s patches are the most frequent cause of death during typhoid fever. (Pg 59)

As the host mounts an inflammatory response at the site of mucosal invasion, Salmonella genes involved in defense against inflammation have to be expressed subsequently to bacterial entry into the epithelium. Coordinated expression of these virulence genes appears to be mediated by PhoPQ, a two-component regulatory system that changes gene expression in response to changes in the external Mg2+ and Ca2+ concentrations. Ca2+ and Mg2+ cations stabilize the outer membrane by neutralizing the negative charge of phosphate groups and bridging adjacent LPS molecules. The intracellular parasitophorous vacuole in which salmonella resides was shown to be low in Mg2+ and Ca2+. In such environments, PhoPQ activates pmrAB, two genes encoding a second two-component regulatory system. Activation of PmrAB increases the substitution of phosphates in both the core oligosaccharide and the lipid A part of the LPS with 4-amino-4-deoxy-L-arabinose, thereby compensating for the lack of Ca2+ and Mg2+ cations. These structural changes in LPS result in increased resistance to bacteriacidal/permeability increasing protein (BPIs), a cationic antibacterial protein that is released by human PMN during inflammation. Furthermore, in response to low Mg2+ and Ca2+ concentrations, PhoPQ activates a second pmrAB-independent pathway, which results in increased resistance to defensins released by recruited PMN and crypdins produced by Paneth cells located in the intestinal crypts. (pg 63)

The major factor for intestinal penetration is encoded by genes that are clustered in a large area (40kb) on the chromosome designated Salmonella pathogenicity island 1 (SPI1) (pg 61) Studies using murine ligated ileal loops revealed that the genes located on SPI1 are necessary for invasion of M cells in the FAE (follicle associated epithelium) of Peyer’s Patches.

Symptoms associated with Salmonella were markedly decreased by treatment with nitrogen mustard, an agent that depletes the polymorphonuclear neutrophil (PMN)… which also inhibits fluid secretion induced by cholera toxin) (pg 62)

In 1958 it was discovered that Salmonella’s ability to agglutinate certain species of erythrocytes and its association between fimbriae and erythrocytes included mannose-containing carbohydrates in lectin-based interactions (pg 35)

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