Visual Analogies of Pathogen Strategies

Visual Analogies of Pathogen Strategies
As presented to the American Society for Microbiology, May 2002

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AN INITIAL ANALOGY Gram-negative bacteria, such as E. coli, might be thought of as capable of wearing two layers of clothing just like people often do - outerwear and undies. And just like with people these layers may be constructed of different fabrics. Additionally, these layers are optional - just like in people. In fact, the usual strain of E.coli that is used in teaching is a "streaker," wearing no clothing at all. The outer layer is called "capsule" or the K-antigen (K = Kapsul in German). The underwear has several names: endotoxin, or lipopolysaccharide (LPS), or the O-antigen (O as in Ohne Hauck, without fuzz in German). The bacteria might also have flagella (sort of like tassels in human-wear), and these are called the H-antigen (H as in Hauck, fuzz in German). Finally, the seams in the layers of clothing in bacteria gape a lot so that underlayers are exposed.

It should then be understood that the body "sees" these invading bacteria by what they "look" like on their outsides - their surfaces. Hence, we talk about surface antigens - those molecules that reside on the exterior of the bacterial cell. (Gram-positive bacteria never wear underwear (!) - because they don't have an outer membrane into which LPS molecules would be attached.)

CONSTRUCTION OF THE MODELS

In constructing each of the following models that analogize a type of pathogenic strategy, you will recognize the pathogen because it wears a black mask. You will click on each link so that you get an image that fits on one piece of paper. Print it out inexpensively in black and white so that you know what size you have to work with. Then you will want to enlarge it perhaps 200% or 250% or more using your printer set-up. Also test that in black and white. Once you are satisfied with the size, print it out at that enlargement in color. (For some, as described below, you will want to print out on various colors of paper.) You may want to use legal-size stationery for this final printing. To increase the "longevity" of your final models, you may wish to cut them out and have them laminated at some office supply store. (Within the "construction comments" are a few links showing other parts you might like to print and cut out. Links in the "pedagogical comments" are for your further understanding, such about bacterial anatomy.)

For use in class, most work very well stuck to the wall or chalkboard by either magnetic tape or velcro, for easy removal. (Magnetic tape and velcro for posters can be purchased at most office supply stores.) Schools built in the past 30 years generally have chalkboards made with a steel backing that holds magnets. Try yours with a refrigerator magnet, if you don't know.

Model's Name Construction Comments Pedagogical Comments

"Hide-Out Model"
(recommend 200%) For this model you can use a clear plastic filing envelope for your eukaryotic cell membrane, and place within it a properly cropped black and white diagram of an animal cell (recommend 100%) Carefully cut out the "critter" along its boundary. You may also want to make a voice balloon (recommend 100%) that says something like: "You can't get me in here!" The balloon can be made out of white paper and taped to the head of the "critter". The "critter" should lie inside the plastic envelope but atop the diagram of a cell's innards. You may forego laminating this one since it will "live" in the plastic envelope. (You will probably not want to enlarge this model for printing.) Plasmodia (malaria) and HIV tend to hide-out in red and white blood cells, respectively. Salmonella (typhoid) hides-out in cells of the intestinal lining, but also move about the body in the blood stream, where they are phagocytized by lymphocytes but not digested. Instead they kill these "professional" phagocytes. Of interest is that some or all Salmonellae can seduce other cells to phagocytize them - even usually rather refractory nerve cells converting them into "non-professional" phagocytes. In all cases the Salmonellae hide-out and are not digested. It is known that Salmonella possess at least 28 genes conferring pathogenicity. What each of these genes do is yet mostly unknown.

"Rambo"
(recommend 250%) Because of the intricacy of the border of this model, you may be excused from cutting it out precisely prior to lamination. Many microbes make enzymes and spew them out into their surroundings to predigest large foods into small and diffusible molecules. Some of these enzymes can harm tissues. Other types of biochemicals are also strewn into the bacteria's environment that block enzymes or other host compounds that were made to combat the microbes. Bacillus anthracis (anthrax) is one such toxin producer. Botulism, gangrene are due to particularly powerful toxins. Even strep throat bacteria produce toxins which make a person's joints ache (rheumatoid arthritis).

"Armored:"
(recommend 200%) This "Superman" or "Wonderwoman" or "Knight" model is one that should be printed on special metallic colored paper, which is available in most craft stores. Buy it so that it is thin enough to run through your computer's printer. The "knight" should be cut out to its border and then laminated. It is hard to picture that some slimy goo can be an armor. In the case of those strains of E. coli, which wear "outer clothes" made of the K5 acidic polysaccharide, the explanation for how it acts as armor is that K5 is a molecule similar to heparin, which inactivates many enzymes that require phosphorylation. Since many of the ensnaring steps in phagocytosis require ATP, and also intra-vacuole digestion of bacteria, bacteria clothed in materials like K5 are relatively resistant to both phagocytosis and digestion.

"Breakaway Jersey"
(recommend 250%) Cut out the football player to it border and laminate it. Also cut out at least one extra jersey. The shoulder-tabs may serve well enough, or you may cut them off and tape some "twist-ties" onto the back of the jersey, which then go over the player's shoulders. The added jersey should be easily removable while the player is adhering to the wall or chalkboard. A number of bacteria produce layers of "clothing" that are so loosely bound to the underlying membranes that they easily tear away if "grabbed" in the encircling tendrils of a phagocyte, such as a macrophage. Not only is the bacterium wiggling due to its flagellar motion, but also due to Brownian motion.

"Decoy Maker"
(recommend 250%) Because of the intricacy of the border of this model, you may be excused from cutting it out precisely prior to lamination. These cells are much like those with breakaway jerseys only that these have exterior layers so loosely attached that they often just slough off in small "sheets." Since antibodies, complement and phagocytes target the "clothing" they often find their efforts directed at empty "shirts" or other swatches of "clothing."

"Quick-Change Artist"
(recommend 230%) To form a series of cut-outs, each one a little larger than the next, make each one 5% larger than the previous one. In this way, the smaller ones can hide behind the larger ones. Double-sided cellophane tape can be used to hold them together. The teacher can practice a bit of slight of hand by holding the composite up before the class, and tell the class (who are playing the role of the immune system) to be on the look-out for a critter wearing - say - a red robe. You pass the composite behind your back and remove and drop the top-most red one, and out it comes wearing some other color. It is thus obvious that you should print each of these on a different color paper. The "faces" can be printed on white paper and pasted onto the robed creatures after they have been cut out. Each critter will have two faces print out: one is the mirror image of the other. The mirror image will prove useful for those of you who use paper that is patterned on one side and white on the reverse. You will want to print on the white side, cut it out, and then find the mirror image face is the one that will fit your colored critter. Finally they are all laminated, and taped together. Lamination is very important here so that the tape removes easily without damaging the model. A number of notable pathogens use this strategy: malaria, gonorrhea, and menigitis, for just three examples. What prompts the nearly simultaneous changing into a new "uniform" is not well understood. You could discuss various "triggers:" do they have an internal clock that tells them when to produce new clothes, or do the communicate with each other by sending out some sort of chemical signal, or might it be triggered by being hit by an antibody? Confusing the "clock" or the signals would be an important advance in the therapeutics of these diseases.

"Masquerade:"
(recommend 250%) This is a very simple model showing cells all wearing sweatshirts emblazened with "H.s." on them because they belong to Homo sapiens. How can a pathogen infiltrate this clan of cells? Of course, by putting on an identical sweatshirt. They may be cut out approximately to its border. The print-out will have the pathogen, a collection of host cells, and the merger of the two. You might start out by showing the bunch of host cells and then bring into view the pathogen, which is wearing the same clothes. Then when you put the pathogen with the cells, you can act silly and say: "Hey, don't hurt me, I'm one of youz guys - I'm family, ya know!" This is a popular strategy adopted by a number of pathogens. Some like meningococcus produce a surface layer of molecules so similar to those covering our normal human cells that the alarm that a pathogen is within us is set off so late that it is too late. If we move the viruses, the adenovirus, which causes severe sore throats, actually clothes itself in fragments of the cell membrane from which it just erupted.

"Stealth"
(recommend 400%) Be "invisible" Of course, while the pathogen might be observable under the microscope, the host organism cannot detect its presence as it may be both masquerading as a host cell, and it may also not be eminating any peculiar molecules which the host might "smell." This is one of the possible scenarios behind why Salmonella might not be digested in food vacuoles of phagocytes.

Model's Name	Construction Comments	Pedagogical Comments
"Hide-Out Model" (recommend 200%)	For this model you can use a clear plastic filing envelope for your eukaryotic cell membrane, and place within it a properly cropped black and white diagram of an animal cell (recommend 100%) Carefully cut out the "critter" along its boundary. You may also want to make a voice balloon (recommend 100%) that says something like: "You can't get me in here!" The balloon can be made out of white paper and taped to the head of the "critter". The "critter" should lie inside the plastic envelope but atop the diagram of a cell's innards. You may forego laminating this one since it will "live" in the plastic envelope. (You will probably not want to enlarge this model for printing.)	Plasmodia (malaria) and HIV tend to hide-out in red and white blood cells, respectively. Salmonella (typhoid) hides-out in cells of the intestinal lining, but also move about the body in the blood stream, where they are phagocytized by lymphocytes but not digested. Instead they kill these "professional" phagocytes. Of interest is that some or all Salmonellae can seduce other cells to phagocytize them - even usually rather refractory nerve cells converting them into "non-professional" phagocytes. In all cases the Salmonellae hide-out and are not digested. It is known that Salmonella possess at least 28 genes conferring pathogenicity. What each of these genes do is yet mostly unknown.
"Rambo" (recommend 250%)	Because of the intricacy of the border of this model, you may be excused from cutting it out precisely prior to lamination.	Many microbes make enzymes and spew them out into their surroundings to predigest large foods into small and diffusible molecules. Some of these enzymes can harm tissues. Other types of biochemicals are also strewn into the bacteria's environment that block enzymes or other host compounds that were made to combat the microbes. Bacillus anthracis (anthrax) is one such toxin producer. Botulism, gangrene are due to particularly powerful toxins. Even strep throat bacteria produce toxins which make a person's joints ache (rheumatoid arthritis).
"Armored:" (recommend 200%)	This "Superman" or "Wonderwoman" or "Knight" model is one that should be printed on special metallic colored paper, which is available in most craft stores. Buy it so that it is thin enough to run through your computer's printer. The "knight" should be cut out to its border and then laminated.	It is hard to picture that some slimy goo can be an armor. In the case of those strains of E. coli, which wear "outer clothes" made of the K5 acidic polysaccharide, the explanation for how it acts as armor is that K5 is a molecule similar to heparin, which inactivates many enzymes that require phosphorylation. Since many of the ensnaring steps in phagocytosis require ATP, and also intra-vacuole digestion of bacteria, bacteria clothed in materials like K5 are relatively resistant to both phagocytosis and digestion.
"Breakaway Jersey" (recommend 250%)	Cut out the football player to it border and laminate it. Also cut out at least one extra jersey. The shoulder-tabs may serve well enough, or you may cut them off and tape some "twist-ties" onto the back of the jersey, which then go over the player's shoulders. The added jersey should be easily removable while the player is adhering to the wall or chalkboard.	A number of bacteria produce layers of "clothing" that are so loosely bound to the underlying membranes that they easily tear away if "grabbed" in the encircling tendrils of a phagocyte, such as a macrophage. Not only is the bacterium wiggling due to its flagellar motion, but also due to Brownian motion.
"Decoy Maker" (recommend 250%)	Because of the intricacy of the border of this model, you may be excused from cutting it out precisely prior to lamination.	These cells are much like those with breakaway jerseys only that these have exterior layers so loosely attached that they often just slough off in small "sheets." Since antibodies, complement and phagocytes target the "clothing" they often find their efforts directed at empty "shirts" or other swatches of "clothing."
"Quick-Change Artist" (recommend 230%)	To form a series of cut-outs, each one a little larger than the next, make each one 5% larger than the previous one. In this way, the smaller ones can hide behind the larger ones. Double-sided cellophane tape can be used to hold them together. The teacher can practice a bit of slight of hand by holding the composite up before the class, and tell the class (who are playing the role of the immune system) to be on the look-out for a critter wearing - say - a red robe. You pass the composite behind your back and remove and drop the top-most red one, and out it comes wearing some other color. It is thus obvious that you should print each of these on a different color paper. The "faces" can be printed on white paper and pasted onto the robed creatures after they have been cut out. Each critter will have two faces print out: one is the mirror image of the other. The mirror image will prove useful for those of you who use paper that is patterned on one side and white on the reverse. You will want to print on the white side, cut it out, and then find the mirror image face is the one that will fit your colored critter. Finally they are all laminated, and taped together. Lamination is very important here so that the tape removes easily without damaging the model.	A number of notable pathogens use this strategy: malaria, gonorrhea, and menigitis, for just three examples. What prompts the nearly simultaneous changing into a new "uniform" is not well understood. You could discuss various "triggers:" do they have an internal clock that tells them when to produce new clothes, or do the communicate with each other by sending out some sort of chemical signal, or might it be triggered by being hit by an antibody? Confusing the "clock" or the signals would be an important advance in the therapeutics of these diseases.
"Masquerade:" (recommend 250%)	This is a very simple model showing cells all wearing sweatshirts emblazened with "H.s." on them because they belong to Homo sapiens. How can a pathogen infiltrate this clan of cells? Of course, by putting on an identical sweatshirt. They may be cut out approximately to its border. The print-out will have the pathogen, a collection of host cells, and the merger of the two. You might start out by showing the bunch of host cells and then bring into view the pathogen, which is wearing the same clothes. Then when you put the pathogen with the cells, you can act silly and say: "Hey, don't hurt me, I'm one of youz guys - I'm family, ya know!"	This is a popular strategy adopted by a number of pathogens. Some like meningococcus produce a surface layer of molecules so similar to those covering our normal human cells that the alarm that a pathogen is within us is set off so late that it is too late. If we move the viruses, the adenovirus, which causes severe sore throats, actually clothes itself in fragments of the cell membrane from which it just erupted.
"Stealth" (recommend 400%)	Be "invisible"	Of course, while the pathogen might be observable under the microscope, the host organism cannot detect its presence as it may be both masquerading as a host cell, and it may also not be eminating any peculiar molecules which the host might "smell." This is one of the possible scenarios behind why Salmonella might not be digested in food vacuoles of phagocytes.

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