Resistance to conventional antitumour therapies and Hypoxia in patients with advanced solid tumours are two major reasons for the failure of conventional anti-tumour therapies. Therefore, it is important to find a new therapeutic method that can overcome these problems. An attenuated anaerobic bacterium, Clostridium novyi- NT, could target Hypoxic and Necrotic areas of tumours causing tumour lysis and stimulating a host anti-tumour immune response. To the best of our knowledge, the combination of bacterial anti-tumour therapy, chemotherapy, radiotherapy and immunotherapy may promote tumour regression, inhibit metastasis and develop a new strategy for the treatment of solid tumours. However, the possible molecular mechanisms of the combined therapies are still the biggest challenge. This review provides an overview of the history of bacterial cancer therapy and the development of a non-lethal strain of Clostridium novyi. Below is a precise definition of Hypoxic conditions in solid tumour tissue. To understand the anticancer effect of Clostridium novyi- NT spores, possible cell death mechanisms were summarised by the enzyme phospholipase C (nt01cx0979), which is secreted by Clostridium novyi- NT spores after germination in tumour tissue. The function of Clostridium novyi- NT spores in stimulating the host immune system to elicit anti-tumour responses was reviewed. Then, the results of anti-tumour combination therapies based on Clostridium novyi- NT spores were compiled. Identifying the molecular mechanisms of Clostridium novyi- NT in treating tumours and inducing cell death in invasive cancer cells, ultimately leading to tumour regression, may develop promising clinical strategies in the combined treatment of solid tumours.
Clostridium perfringens is a Gram-positive anaerobic bacterium which is divided based on major toxins into five types (A-E). C. perfringens type D causes fatal enterotoxaemia (pulpy kidney) in sheep and goats that causes heavy economic losses in domestic animals. However current enterotoxaemia vaccine has been effective in controlling of disease; Strategies for the development of effective vaccine can be achieved by the production of new generation experimental vaccines. The aim of this study was cloning and expression of epsilon toxin of C. perfringens type D in E. coli Rosetta (DE3) to improve of the immunity. Epsilon toxin gene was cloned into pJET1.2/blunt vector and pET22b (+) expression vector and finally transformed into E. coli Rosetta competent cells (DE3). The result showed that the epsilon gene of C. perfringens type D can be cloned and expressed in E. coli RosettaTM (DE3) successfully. E. coli was suitable host for the expression of C. perfringens epsilon toxin. Clearly, future research is open for further refinement of the study.
Clostridium septicum is the causative agent of the acute fetal disease braxy and gas gangrene with major economic losses in the dairy industry. Accurate and rapid detection is great importance in this regard. Vaccination is an effective process for protection against C. septicum infection. It is necessary to identify and evaluate toxigenic Iranian isolates to produce a vaccine. This study aimed to detect Iranian isolates and evaluate toxigenic isolates as candidates for vaccine production. To this end, a total of 17 samples of animals, clinically suspected to braxy and malignant edema, were obtained. All samples were then cultured on media and microbiological and biochemical tests were performed on the colonies. The test results were confirmed by PCR amplification of the alpha-toxin gene. The toxigenic isolates were then evaluated using MLD. The experimental vaccine was produced and evaluated according to the British Pharmacopoeia Standard. According to the results, out of 17 samples, 15 samples were considered C. septicum. All samples were confirmed by PCR amplification. The most toxigenic isolate was used for experimental vaccine production. The result was successful. The Iranian isolate could be, therefore, used for vaccine production although further studies should be conducted in this regard.
Clostridia are Gram-positive anaerobic, spore-forming rods, found in soil, water as well as gastro-intestinal tract of human and animals worldwide. Clostridial infections are among the most prevalent diseases in Iran. Clostridium causes botulism, tetanus, food poisoning, wound infections, enterotoxaemia, gas gangrene, necrotic enteritis, pseudomembranous colitis, blackleg and black disease. Clostridium also causes several diseases affecting the livestock and poultry industries throughout the world. Vaccination against clostridial infection is effective in immunization of domestic animals and birds. This review discusses clostridial infection and the development of vaccines against their infection in Iran. The last reported outbreaks of blackleg, black disease and enterotoxaemia occurred years ago, so these vaccines have been produced since the 1960s using traditional and conventional methods. In recent years, molecular biology methods have been developed and applied to the identification of clostridial diseases among animals. In this study, molecular cloning strategies for the major toxins of Clostridium species, for development of recombinant vaccines, were designed and evaluated. In vivo studies indicate that the recombinant vaccines will increase immunity against disease in laboratory animals. These experimental vaccines can thus be used in future pilot studies in Iran. This review article presents current knowledge regarding C. perfringens, C. novyi, C. septicum and C. chauvoei in the veterinary industry in Iran.
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