The relationship between a pathogen and the host it infects is complex and varied
In this excerpt from The Infectious Microbe, author William Firshein explores microbial diseases as relationships between microorganisms and pathogens.
Although there is a strong belief by most of us that microbial diseases are always dangerous and are a one-way street toward sickness or death, that is many times not the case. Rather, a microbial “disease” is best characterized as a “relationship” between the microorganism (called a pathogen; that is, a microorganism capable of causing a disease) and the host (the individual with whom it comes in contact, or infects). Because the term “pathogen” implies a successful outcome for the microorganism, which isn’t always the case, a microbial infection is more aptly described as a “host-parasite” relationship, where “parasite” is defined as any organism that is sheltered or feeds in a different organism.
It does not necessarily imply that the infection will always lead to a successful outcome for the parasite. In fact, there are three outcomes of an infection by a microorganism: (1) the parasite becomes a pathogen and overcomes the immune defenses of the host, (2) the host’s immune defenses overcome the ability of the potential pathogen to cause the disease, or (3) most intriguing, the parasite (or potential pathogen) and the host survive together (why in the world would they want to do that?). These are the three extremes for this relationship, and they depend on many, many diverse factors. For example, potential pathogens fall into two basic types, primary and opportunistic. The former can often cause diseases among a definite percentage of infected individuals, while the latter causes diseases only in individuals whose immune systems are temporarily or permanently defective.
Nevertheless, an opportunistic pathogen in one host can be a primary one in another. What makes a pathogen successful? Basically, it is a combination of its own “prowess”; that is, an ability to produce virulence (or poisonous) factors that damage the host, and the “weakness” of the host’s immune defenses. In some cases the immune defense system is strong, but the virulence factors produced by the pathogen are still more powerful. Nevertheless, it is not always the case that success will result in the demise of the host. In most cases, the host becomes sick but eventually rallies to overcome the virulence of the pathogen, resulting in its destruction, although in many cases, the pathogen can exist in low numbers in various parts of the body. Even if the host’s immune system is compromised this outcome can occur, but it will take longer. It is like a race, one that pits the specific response of the immune system to the pathogen (which takes time to develop) against the growth and multiplication of the pathogen (which also takes time).
What makes a pathogen successful? Basically, it is a combination of its own “prowess”; that is, an ability to produce virulence (or poisonous) factors that damage the host, and the “weakness” of the host’s immune defenses.
However, it is the third outcome, where a relationship is established between the host and the parasite, that has led to new thinking about pathogenicity. In one sense, it does not make evolutionary “sense” for the potential pathogen to “destroy” its host, because without a suitable host, the pathogen too will become extinct. Thus, in the long run, pathogens have an “interest” in ensuring the host’s survival. As a famous Nobel Prize microbiologist, Joshua Lederberg, has written, “We should think of each host and its parasite as a super organism” where “domesticating the host is the better long term strategy for the parasite” (imagine humans being “domesticated” by microorganisms!). Thus, many diseases have evolved into “milder” sicknesses,such as Streptococcus pyogenes. This particular microorganism causes, among other ailments, the common “strep” sore throat. Yet, during the twentieth century, infections that started with this symptom progressed many times to scarlet fever, which could be fatal, and further to rheumatic fever, a debilitating chronic disease that could permanently damage the heart.
In a strange twist of fate, in 1901 the famous Rockefeller Institute for Medical Research was founded by John D. Rockefeller because his grandson died of scarlet fever and he was determined to find ways to treat this and other diseases such as pneumonia, for which there were no cures. Today, although these diseases still exist, they are, except for the “strep” throat, exceedingly rare because of the genetic alteration in the ability of this streptococcus to produce one or more virulence factors. Nevertheless, such changes would probably have not led to the survival of the less dangerous microorganism unless it was advantageous, as, for example, not destroying its host.
Of interest is that such changes may also occur within a relatively short time period. A striking example could involve one of the most dreaded diseases of our time, caused by the HIV virus (or human immunodeficiency virus), which eventually leads to AIDS (or acquired immunodeficiency syndrome). Although the results are by necessity preliminary, it appears that HIV caused a more rapid progression to full-blown AIDS during the late 1970s and 1980s than it does now (2000–present). Newer samples of the virus do not develop well in the host cells (lymphocytes, which are white blood cells) they infect and are not as resistant to immune attack as those preserved from patients in those previous years. Thus, passage of the virus in the general human population has possibly made it “weaker” with time, perhaps reaching an “equilibrium” with its host to “permit” a longer survival period.
This, of course, is not meant to imply that the “virus” has some kind of purposeful thought process; rather, it suggests some kind of natural process that has evolved with time that affects both the host and the parasite.
This, of course, is not meant to imply that the “virus” has some kind of purposeful thought process; rather, it suggests some kind of natural process that has evolved with time that affects both the host and the parasite. This process is called “natural selection.” Indeed, there are numerous examples of a host modification that can render it more resistant to a particular pathogen, even if the modification results in a genetic defect. One such classic example involves the parasite that causes malaria (a protozoan — still a microorganism). It has great difficulty infecting those individuals who have sickle cell anemia (in which red blood cells are deformed), because as part of its life cycle, the parasite must grow in normal red blood cells. Another example concerns the virus we mentioned above — HIV. In order to infect susceptible lymphocytes, it must first attach to certain “receptor” sites on the surface of the lymphocyte. In the alteration, which is not known to be harmful to the host, the components that make up the receptor sites have been changed by some type of genetic event (mutation?) during evolution of some of our ancestors, which prevents the virus from binding. Thus, this subset of our population is immune to the development of AIDS or at least is more resistant to the development of AIDS.
William Firshein is the Daniel Ayers Professor of Biology Emeritus who chaired the Department of Biology at Wesleyan University for six years. He has published over 75 original research papers concerning microbial pathogenicity and was awarded several million dollars from both governmental and private agencies to support his research. He has taught over 6000 undergraduate and graduate students during his 47-year tenure at Wesleyan, as well as presenting numerous seminars at various universities and meetings.
