"Bacterial cells are generally observed as vegetative cells, but some genera of bacteria have the ability to form endospores, structures that essentially protect the bacterial genome in a dormant state when environmental conditions are unfavorable. Endospores, not to be confused with the reproductive spores formed by fungi, allow some bacterial cells to survive long periods without food or water, as well as exposure to chemicals, extreme temperatures, and even radiation. Vegetative cells are sensitive to extreme temperatures and radiation, have normal water content and enzymatic activity, and are capable of active growth and metabolism. Endospores are resistant to extreme temperatures and radiation, are dehydrated with no metabolic activity, and are dormant with no growth or metabolic activity. Vegetative cells are gram-positive, whereas endospores do not absorb Gram stain and require special endospore stains. The process by which vegetative cells transform into endospores is called sporulation, and it generally begins when nutrients become depleted or environmental conditions become otherwise unfavorable. The process begins with the formation of a septum in the vegetative bacterial cell. The septum divides the cell asymmetrically, separating a DNA forespore from the mother cell. The forespore, which will form the core of the endospore, is essentially a copy of the cell’s chromosomes and is separated from the mother cell by a second membrane. A cortex gradually forms around the forespore by laying down layers of calcium and dipicolinic acid between membranes. A protein spore coat then forms around the cortex while the DNA of the mother cell disintegrates. Further maturation of the endospore occurs with the formation of an outermost exosporium. The endospore is released upon disintegration of the mother cell, completing sporulation. Not all bacteria have the ability to form endospores; however, there are a number of clinically significant endospore-forming, gram-positive bacteria of the genera Bacillus and Clostridium. These include B. anthracis, the causative agent of anthrax, which produces endospores capable of surviving for many decades; C. tetani, which causes tetanus; C. difficile, which causes pseudomembranous colitis; C. perfringens, which causes gas gangrene; and C. botulinum, which causes botulism. Pathogens such as these are particularly difficult to combat because their endospores are so hard to kill."