In 1876, Robert Koch provided the first proof that bacteria caused disease. He accomplished this while in a race with Louis Pasteur to determine the cause of anthrax, which was destroying the cattle and sheep in Europe. (This is the same organism that is reportedly being cultured for bacterial warfare.) He (1) detected a rod-shaped bacteria, Bacillus anthracis, in the blood of cattle that had died of anthrax; (2) cultured the bacteria in nutrients; (3) injected bacteria from the cultures into healthy cattle, which then became sick and died from anthrax; and then (4) detected the same bacteria in the blood of the cattle that he had infected. This experimental protocol formed the basis of Koch's postulates, which have been used to trace the causes of disease since then. The following summarizes those postulates:
As with almost every, if not all, postulates in science, there are limitations and exceptions to Koch's postulates. For example, virulent strains of the bacteria that cause syphilis, Treponema pallidum, or leprosy, Mycobacterium leprae, have never been cultured in artificial media. Similarly, some infectious diseases, such as nephritis, may be caused by several different pathogens; and some pathogens can cause several different disease conditions, including Streptococcus pyogenes that can cause sore throat, scarlet fever, erysipelas (skin infections), puerperal fever, and osteomyleitis (bone inflammation). Finally, there is the ethical question of intentionally inoculating humans with infectious agents for some diseases that cause disease in humans and have no other known host (e.g., HIV).
There are 4 principal mechanisms for bacterial toxicity. (1) The physical presence of the bacteria may cause direct damage to infected and adjacent cells and tissue. (2) The bacteria may produce toxins that damage the adjacent area. (3) The bacteria may produce toxins that are transported through the blood and lymph systems, and then damage more remote areas. (4) The bacterial infection may induce hypersensivity reactions.
Some bacteria (E. coli, Shigella, Salmonella, and N. gonorrhoeae) induce host epithelial cells to engulf them, and other bacteria may penetrate host cells by excreting enzymes that degrade the cell wall or by physically penetrating the cell wall. These penetrationsmay damage the host cell, as can the subsequent multiplication of bacteria within the host cell. However, most damage from bacteria is caused by the toxins that they generate.
Bacteria produce 2 types of toxins: exotoxins and endotoxins. Exotoxins are are produced within living bacteria, and then released into the surrounding medium. Endotoxins are a component of the outer portion of a bacterial cell wall, and are released when the bacteria dies and the cell wall disintegrates.
There are 3 types of exotoxins: cytotoxins, neurotoxins, and enterotoxins. (1) Cytotoxins kill the host cell or disrupt its normal functions. An example is Streptococcus pyogenes, which sysnthesizes three types of cytotoxins, which are known as erythrotoxins because they damage red blood cells. This accounts Scarlet fever, which is characterized by the resultant red rash caused by the damage to blood capillaries. (2) Neurotoxins are produced by other bacteria, including Clostridium botulinum and Vibrio cholerae. The botulism toxin causes paralysis by binding to nerve cells, which prevents the release of the neurotransmitter, acetylcholine, at the neuromuscular junction. The cholera toxin (as well as some strains of E. coli) binds to the plasma membranes of epithelial cells lining the small intestine and induce the cells to dischareg large amounts of fluids and electrolytes. This results in severe diarrhea and vomiting.
Endotoxins from different bacteria all have the same effects, once they are released with the death of those bacteria. These effects include fever, chills, weakness, aches, blood clots, shock, and death. The fever (pyrogenic response) is attributed to the induction of a protein, interleukin-1, that cause the hypothalmus to increase the body temperature. Septic shock occurs when endotoxins induce the secretion of a polypeptide, tumor necrosis factor (TNF) or cachectin, which alters metabolism and may damage blood capillaries (their permeability increases and they lose fluids). This results in a drop in blood pressure, wihich causes shock, and also damages the kidneys , lung, and gastrointestinal tract. There is also a breal down in the blood brain barrier, which allows bacteria enter from the bloodstraem. Among the bacteria that produce endotoxins are Salmonella typhi (thyphoid fever), Proteus spp. (urinary tract infections), and Neisseria meningitidis (meningococcal meningitis).
Finally, hypersensitivity occurs when the antigenic response is greater than normal. It commonly occurs in individuals that have been sensitized from a previous exposure(s0 to an antigen or allergen. This sensitization causes the individuals immune system to react to a subsequent exposure in a manner that is, itself, damaging. One example of this response is an anaphylactic (literally the opposite of protected) reaction.
Tortora, G.J., B.R. Funke, and C.L. Case. 1997. Microbiology: An Introduction. 6th Edition. Addison Wesley Longman, Inc., Menlo Park, CA. pp. 832.