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The spore coat endows bacterial spores with remarkable resistance to physical and chemical agents and allows them to persist in nature for centuries ( 11, 17, 57).Ītomic force microscopy (AFM) has been used to study the architecture and assembly of a wide range of biological systems ( 18, 20, 23, 24, 27, 34, 37, 45). During the outgrowth stage, macromolecular synthesis in the spore converts the germinated spore into a growing cell ( 35, 46). The outgrowth stage starts with the initiation of spore metabolism. Germination is a well-defined process of conversion of a dormant spore into a metabolically active form ( 46). Despite this long history and the importance of clostridia spores in other medical contexts, there have been relatively few studies of either the nature of the germination and outgrowth processes or the structure of the spore coat. Many of these attempts used various strains of clostridia. Such therapeutic approaches were first attempted more than 50 years ago and have continued sporadically since that time. novyi NT is therefore one of the most promising bacterial agents for cancer therapeutics that have been described in the past few years ( 55). novyi NT spores are injected into mice, the spores exclusively germinate in tumors and spare other tissues, even in aged animals or those with ischemic myocardial lesions ( 16).Ĭ. novyi NT spores into tumor-bearing mice was found to successfully eradicate large tumors, either in combination with radiation therapy ( 7) and chemotherapy ( 13) or by itself, since it can induce a potent immune response ( 1). novyi NT and devoid of the alpha-toxin, was generated. To reduce systemic toxicity, an attenuated strain, called C. novyi is attributed to the lethal alpha-toxin ( 6). It can cause infections leading to gas gangrene in humans, particularly after traumatic wounds or illicit drug use, and can also infect domestic animals, particularly sheep ( 22). novyi NT, these studies document the presence of proteinaceous growth spirals in a biological organism.Ĭlostridium novyi is a motile, spore-forming, gram-variable (gram positive in young cultures, often gram negative in older cultures) anaerobic bacterium. In addition to their implications for understanding the biology of C. During germination and outgrowth, the honeycomb layers, as well as the underlying spore coat and undercoat layers, sequentially dissolved until the vegetative cell was released. Moreover, the spore coat layers had apparently self-assembled, and this assembly was likely to be governed by crystal growth principles. We found that the spores are surrounded by an amorphous layer intertwined with honeycomb parasporal layers. Toward this end, we have used both transmission electron microscopy and atomic force microscopy to determine the structure of both dormant and germinating spores. Future progress in this area will benefit from a better understanding of the germination and outgrowth processes that are essential for the tumorilytic properties of these spores. EVOLVE Your Creature through Five Stages: It's survival of the funnest as your choices reverberate through generations and ultimately decide the fate of your civilization.Spores of the anaerobic bacterium Clostridium novyi NT are able to germinate in and destroy hypoxic regions of tumors in experimental animals.CREATE Your Universe from Microscopic to Macrocosmic: From tide pool amoebas to thriving civilizations to intergalactic starships, everything is in your hands.
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Spore gives you a variety of powerful yet easy-to-use creation tools so you can create every aspect of your universe: creatures, vehicles, buildings, and even starships. What you do with your universe is up to you. You can play how you choose: Start in Cell and nurture one species from humble tidepool organism to intergalactic traveler, or jump straight in and build tribes or civilizations on new planets. Each stage has its own unique style, challenges, and goals. About This Game From Single Cell to Galactic God, evolve in a universe of your own creations.Play through Spore's five evolutionary stages: Cell, Creature, Tribe, Civilization, and Space.