A tumour therapy is proposed based on attenuated Salmonella typhimurium VNP20047 expressing the Escherichia coli cytosine deaminase gene. VNP20047 was administered intravenously to B16(F10) melanoma-bearing C57BL/6 mice. VNP20047 proliferated within tumours and livers regardless of the initial inoculum dose. After 10 days the number of bacteria increased in livers up to 4.2 × 106 cfu/g and decreased in tumours down to 5.9 × 106 cfu/g. VNP20047 at 1 × 105 cfu/mouse, when combined with 5-fluorocytosine, inhibited tumour growth by 85% without prolonging animal survival. Histology studies revealed severe lesions in tumours and livers. These data suggest that S. typhimurium VNP20047 induced inflammatory responses, even though the strain was attenuated.
The aim of the study was to isolate and identify the extent of Salmonella and Shigella induced diarrhoea in children under five and to determine their antibacterial susceptibility patterns. The method of investigation was a cross-sectional study. Samples were collected from children less than five years old afflicted with diarrhoea coming for treatment at Thika Level Five Hospital, Kiambu County. A total of 80 stool samples were collected. These were specifically examined for Shigella and Salmonella. In doing so, the samples were cultured in MacConkey and Xylose lactose deoxycholate (XLD) agar. The plates were subsequently incubated aerobically at 37 °C overnight. After incubation, suspected Salmonella and Shigella colonies were identified morphologically, marked and the colonies inoculated to biochemical tests for species identification as described in the Medical Laboratory Manual. Following this, colonies derived from purity plating through biochemical testing were sub-cultured onto nutrient agar to obtain pure colonies. The obtained pure colonies were then used to perform susceptibility tests to commonly prescribed antibacterial drugs, including Gentamicin, Ciproflaxicin and Erythromycin. Results showed 10 (12.5%) confirmed positive isolates, where 6 (60%) were Salmonella and 4 (40%) Shigella. With respect to age, both isolates were found to be concentrated more at ages of 1-4 years. Herein, Salmonella – 1-2 years (33.33%), - 2-3years (50%); Shigella – 1-2 years (50%), - 2-3 years (25%). From the study, sex distribution (male or female) of the host isolates was equal (50-50%). Moreover, Ciprofloxacin and Gentamycin were the most potent antibiotics, whereas Ampicillin, Erythromycin, Cotrimoxazole and Sulfamethoxazole were highly resisted. According to study results, Quinolones and Aminogylcosides are the antibiotics of choice for severe diarrhoea illnesses caused by Salmonella and Shigella.
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Salmonella enterica serovar typhimurium was stressed by incubation in seawater microcosms for seventeen years. The microcosms were prepared in such a way as to allow progressive evaporation of the water. Despite being introduced into the sterile seawater at very high concentrations, the Salmonella rapidly declined to levels undetectable by plate counts on nutrient agar. After two years of starvation, about half of the seawater volume had evaporated from each microcosm, and salt crystals appeared. Inoculation of the salty suspension did not result in any culturable strains in selective and non-selective media. However, incubation of samples in nutrient-rich broth, without supplemental growth factors, allowed resuscitation of stressed cells, yielding colonies that remained viable for extended periods of time. After three years the total volume of water had evaporated from each microcosm, and only salt crystals remained. These microcosms were then incubated at room temperature for seventeen years. Resuscitation of VBNC Salmonella from the salt crystals was conducted in vitro and in vivo; recovery occurring after incubation in both nutrient broth and in mice. Recovery occurred in the Salmonella
An O-specific polysaccharide containing D-galactose, D-mannose and L-rhamnose was obtained by mild acid hydrolysis of the lipopolysaccharide of the Salmonella Anatum bacterium. The structure of the polymeric O-antigen was studied by composition analysis and by 1D and 2D, 1H and 13C NMR spectroscopy. The repeating unit of the polymer was identified as a linear trisaccharide with the structure shown below, in which the galactose residue was partially O-ac ety lat ed at C-6; this was re spon si ble for the mol e cule’s structural heterogeneity. → 3)-D-Galp-(1)-D-Manp-(1)-alfa-L-Rhap-(1→ 6 OAc (75%).
Bacterial cancer therapy is a concept more than 100 years old - yet, all things considered, it is still in early development. While the use of many passive therapeutics is hindered by the complexity of tumor biology, bacteria offer unique features that can overcome these limitations. Microbial metabolism, motility and sensitivity can lead to site-specific treatment, highly focused on the tumor and safe to other tissues. Activation of tumor-specific immunity is another important mechanism of such therapies. Several bacterial strains have been evaluated as cancer therapeutics so far, Salmonella Typhimurium being one of the most promising. S. Typhimurium and its derivatives have been used both as direct tumoricidal agents and as cancer vaccine vectors. VNP20009, an attenuated mutant of S. Typhimurium, shows significant native toxicity against murine tumors and was studied in a first-in-man phase I clinical trial for toxicity and anticancer activity. While proved to be safe in cancer patients, insufficient tumor colonization of VNP20009 was identified as a major limitation for further clinical development. Antibody-fragment-based targeting of cancer cells is one of the few approaches proposed to overcome this drawback.