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Microbial Biotechnology May 2020Bacterial vectors, as microscopic living 'robotic factories', can be reprogrammed into microscopic living 'robotic factories', using a top-down bioengineering approach... (Review)
Review
Bacterial vectors, as microscopic living 'robotic factories', can be reprogrammed into microscopic living 'robotic factories', using a top-down bioengineering approach to produce and deliver anticancer agents. Most of the current research has focused on bacterial species such as Salmonella typhimurium or Clostridium novyi. However, Escherichia coli Nissle 1917 (EcN) is another promising candidate with probiotic properties. EcN offers increased applicability for cancer treatment with the development of new molecular biology and complete genome sequencing techniques. In this review, we discuss the genetics and physical properties of EcN. We also summarize and analyse recent studies regarding tumour therapy mediated by EcN. Many challenges remain in the development of more promising strategies for combatting cancer with EcN.
Topics: Antineoplastic Agents; Bioengineering; Escherichia coli; Humans; Molecular Targeted Therapy; Neoplasms; Organisms, Genetically Modified; Probiotics
PubMed: 31863567
DOI: 10.1111/1751-7915.13523 -
Biochimica Et Biophysica Acta.... Sep 2021Studies of the lipidomes of twenty-one species of clostridia have revealed considerable diversity. Even among those species now defined as Clostridium sensu stricto,... (Review)
Review
Studies of the lipidomes of twenty-one species of clostridia have revealed considerable diversity. Even among those species now defined as Clostridium sensu stricto, which are related to Clostridium butyricum, the type species, lipid analysis has shown that a number of distinct clades have characteristic polar lipids. All species of Clostridium sensu stricto have phosphatidylethanolamine, phosphatidylglycerol and cardiolipin which are present as all acyl or alk-1'-enyl acyl (plasmalogen) species. In addition, almost every clade has specialized polar lipids. For example, the group closely related to Clostridium beijerinckii and several other solventogenic species has glycerol acetals of plasmenylethanolamine, which protects the membrane bilayer arrangement when the lipids are highly unsaturated or in the presence of solvents. The group related to Clostridium novyi has aminoacyl-phosphatidylglycerol, which protects these pathogens from cationic antimicrobial peptides (CAMPs) of innate immunity. Clostridium botulinum species, which fall into several groups, align with these clades, and have the same specific lipids. This review will present the current state of knowledge on clostridial lipids.
Topics: Clostridium; Lipidomics
PubMed: 33974975
DOI: 10.1016/j.bbalip.2021.158966 -
Genes & Diseases Jun 2016The attenuated anaerobic bacterium -NT (-NT) is known for its ability to precisely germinate in and eradicate treatment-resistant hypoxic tumors in various experimental... (Review)
Review
The attenuated anaerobic bacterium -NT (-NT) is known for its ability to precisely germinate in and eradicate treatment-resistant hypoxic tumors in various experimental animal models and spontaneously occurring canine sarcomas. In this article, we review the therapeutic and toxicologic aspects of -NT therapy, key challenges and limitations, and promising strategies to optimize its performance recombinant DNA technology and immunotherapeutic approaches, to establish -NT as an essential tool in cancer therapy.
PubMed: 30258882
DOI: 10.1016/j.gendis.2016.01.003 -
Vaccines Feb 2022The clostridial diseases of horses can be divided into three major groups: enteric/enterotoxic, histotoxic, and neurotoxic. The main enteric/enterotoxic diseases include... (Review)
Review
The clostridial diseases of horses can be divided into three major groups: enteric/enterotoxic, histotoxic, and neurotoxic. The main enteric/enterotoxic diseases include those produced by type C and , both of which are characterized by enterocolitis. The main histotoxic diseases are gas gangrene, Tyzzer disease, and infectious necrotic hepatitis. Gas gangrene is produced by one or more of the following microorganisms: type A, , and type A, and it is characterized by necrotizing cellulitis and/or myositis. Tyzzer disease is produced by and is mainly characterized by multifocal necrotizing hepatitis. Infectious necrotic hepatitis is produced by type B and is characterized by focal necrotizing hepatitis. The main neurotoxic clostridial diseases are tetanus and botulism, which are produced by and , respectively. Tetanus is characterized by spastic paralysis and botulism by flaccid paralysis. Neither disease present with specific gross or microscopic lesions. The pathogenesis of clostridial diseases involves the production of toxins. Confirming a diagnosis of some of the clostridial diseases of horses is sometimes difficult, mainly because some agents can be present in tissues of normal animals. This paper reviews the main clostridial diseases of horses.
PubMed: 35214776
DOI: 10.3390/vaccines10020318 -
Neuro-oncology Advances 2022Hypoxia is a prominent feature of solid tumors and can function as fertile environment for oncolytic anaerobic bacteria such as -NT (-NT) where it can induce tumor...
BACKGROUND
Hypoxia is a prominent feature of solid tumors and can function as fertile environment for oncolytic anaerobic bacteria such as -NT (-NT) where it can induce tumor destruction in mice and patients. However, two major obstacles have limited its use, namely the host inflammatory response and the incomplete clearance of normoxic tumor areas.
METHODS
In this study, we first used a subcutaneous tumor model of a glioblastoma (GBM) cell line in immunocompetent mice to investigate the local distribution of tumor hypoxia, kinetics of -NT germination and spread, and the local host immune response. We subsequently applied the acquired knowledge to develop a -NT therapy in an orthotopic rabbit brain tumor model.
RESULTS
We found that local accumulation of granular leukocytes, mainly neutrophils, could impede the spread of bacteria through the tumor and prevent complete oncolysis. Depletion of neutrophils via anti-Ly6G antibody or bone marrow suppression using hydroxyurea significantly improved tumor clearance. We then applied this approach to rabbits implanted with an aggressive intracranial brain tumor and achieved long-term survival in majority of the animals without apparent toxicity.
CONCLUSION
These results indicated that depleting neutrophils can greatly enhance the safety and efficacy of -NT cancer therapy for brain tumors.
PubMed: 35118381
DOI: 10.1093/noajnl/vdab184 -
Tropical Animal Health and Production Apr 2021Clostridium is a Gram-positive, rod-shaped, anaerobic, and spore-forming bacterium, which is found in the surrounding environments throughout the world. Clostridium... (Review)
Review
Clostridium is a Gram-positive, rod-shaped, anaerobic, and spore-forming bacterium, which is found in the surrounding environments throughout the world. Clostridium species cause botulism, tetanus, enterotoxaemia, gas gangrene, necrotic enteritis, pseudomembranous colitis, blackleg, and black disease. Clostridium infection causes severe economic losses in livestock and poultry industries. Vaccination seems to be an effective way to control Clostridial diseases. This review discusses the toxins and vaccine development of the most common pathogenic Clostridium species in animals, including Clostridium perfringens, Clostridium novyi, Clostridium chauvoei, and Clostridium septicum. In this comprehensive study, we will review different kinds of clostridial toxins and the vaccines that are experimentally or practically available and will give a short description on each vaccine focusing on its applications, advantages, and disadvantages.
Topics: Animals; Clostridium; Clostridium Infections; Clostridium perfringens; Vaccination
PubMed: 33891221
DOI: 10.1007/s11250-021-02728-w -
Journal of Cancer Research and... 2018Side effects associated with conventional anticancer therapies have prompted the new idea of solid tumor treatment strategy. One of them is using bacteria explored as... (Meta-Analysis)
Meta-Analysis Review
Side effects associated with conventional anticancer therapies have prompted the new idea of solid tumor treatment strategy. One of them is using bacteria explored as potential antitumor agents over more than one century. Notably, the ideal therapy is a specifical target to tumors with limited toxicity. Here, we take "Clostridium novyi" for the search keyword in the PubMed from 2000 to 2015 and describe that C. novyi-NT spores act as "Trojan horse" for bacteriolytic therapy. This therapy is based on the fact that the live and attenuated obligate anaerobic bacteria are capable of binary fission selectively in anoxic areas of solid tumors and direct tumoricidal effects. Our succinct review mainly concentrates on the potential mechanisms of combination bacteriolytic therapy, an effective and safe tumor therapy with the help of C. novyi-NT. Importantly, C. novyi-NT spores were shown to induce solid tumor regression and exhibit the property to initiate an immune response. Therefore, C. novyi-NT spores should be an effective and safe tumor therapy.
Topics: Animals; Antineoplastic Agents; Biological Therapy; Clostridium; Humans; Neoplasms; Spores, Bacterial
PubMed: 29578142
DOI: 10.4103/0973-1482.204841 -
Communications Biology Sep 2022Clostridium novyi alpha-toxin (Tcnα) is a potent exotoxin that induces severe symptoms including gas gangrene, myositis, necrotic hepatitis, and sepsis. Tcnα binds to...
Clostridium novyi alpha-toxin (Tcnα) is a potent exotoxin that induces severe symptoms including gas gangrene, myositis, necrotic hepatitis, and sepsis. Tcnα binds to sulfated glycosaminoglycans (sGAG) for cell-surface attachment and utilizes low-density lipoprotein receptor (LDLR) for rapid entry. However, it was also shown that Tcnα may use alternative entry receptors other than LDLR. Here, we define that LRP1 and Megalin can also facilitate the cellular entry of Tcnα by employing reconstitutive LDLR family proteins. LDLR, LRP1, and Megalin recognize Tcnα via their ligand-binding domains (also known as LDL receptor type A repeats). Notably, LDLR and LRP1 have contrasting expression levels in many different cells, thus the dominant entry receptor for Tcnα could be cell-type dependent. These findings together increase our knowledge of the Tcnα actions and further help to understand the pathogenesis of C. novyi infection-associated diseases.
Topics: Bacterial Toxins; Biological Transport; Carrier Proteins; Low Density Lipoprotein Receptor-Related Protein-2; Receptors, LDL
PubMed: 36064583
DOI: 10.1038/s42003-022-03873-0 -
Oncology Letters Feb 2021Several solid tumors (for example leiomyosarcoma, melanoma and hepatocellular carcinoma) possess areas of hypoxia, which underlies one of the primary reasons of failure... (Review)
Review
Several solid tumors (for example leiomyosarcoma, melanoma and hepatocellular carcinoma) possess areas of hypoxia, which underlies one of the primary reasons of failure of conventional anticancer therapies. The areas of poor vascularization are insensitive to radiotherapy and chemotherapeutic drugs. Conversely, the hypoxic regions of tumors provide an ideal environment for anaerobic bacteria. The attenuated anaerobic bacterium, Clostridium novyi-NT (C. novyi-NT), is highly sensitive to oxygen and can target the destruction of hypoxic and necrotic areas of tumors, inducing oncolysis and characteristics indicative of an immune response. Theoretically, chemotherapy, radiotherapy and immunotherapy combined with bacterial therapy can be used as a novel means of treating solid tumors, promoting tumor regression and inhibiting metastasis formation with a notable beneficial effect. The present review discusses the molecular mechanisms of combined bacteriolytic therapy, predominantly focusing on C. novyi-NT, and summarizes the findings of previous studies on experimental animal models, including its efficacy and safety via different drug delivery routes. This strategy has great potential to overcome the limitations of conventional cancer therapy, resulting in improved treatments, and thus potentially improved outcomes for patients.
PubMed: 33376543
DOI: 10.3892/ol.2020.12371 -
Journal of Veterinary Diagnostic... Mar 2020Clostridia can cause hepatic damage in domestic livestock, and wild and laboratory animals. type B causes infectious necrotic hepatitis (INH) in sheep and less... (Review)
Review
Clostridia can cause hepatic damage in domestic livestock, and wild and laboratory animals. type B causes infectious necrotic hepatitis (INH) in sheep and less frequently in other species. Spores of type B can be present in soil; after ingestion, they reach the liver via portal circulation where they persist in phagocytic cells. Following liver damage, frequently caused by migrating parasites, local anaerobic conditions allow germination of the clostridial spores and production of toxins. type B alpha toxin causes necrotizing hepatitis and extensive edema, congestion, and hemorrhage in multiple organs. causes bacillary hemoglobinuria (BH) in cattle, sheep, and rarely, horses. Beta toxin is the main virulence factor of , causing hepatic necrosis and hemolysis. , the causal agent of Tyzzer disease (TD), is the only gram-negative and obligate intracellular pathogenic clostridia. TD occurs in multiple species, but it is more frequent in foals, lagomorphs, and laboratory animals. The mode of transmission is fecal-oral, with ingestion of spores from a fecal-contaminated environment. In affected animals, proliferates in the intestinal mucosa, resulting in necrosis, and then disseminates to the liver and other organs. Virulence factors for this microorganism have not been identified, to date. Given the peracute or acute nature of clostridial hepatitis in animals, treatment is rarely effective. However, INH and BH can be prevented, and should be controlled by vaccination and control of liver flukes. To date, no vaccine is available to prevent TD.
Topics: Animals; Clostridiales; Clostridium; Clostridium Infections; Hemoglobinuria; Hepatitis, Animal; Necrosis
PubMed: 31735127
DOI: 10.1177/1040638719886567