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EDITORIAL
The Microbe's View of Infection
1 August 1998 | Volume 129 Issue 3 | Pages 247-248
The First International Conference on Emerging Infectious Diseases was held in Atlanta, Georgia, on 8 to 11 March 1998. It was organized by the Centers for Disease Control and Prevention with the sponsorship of the American Society for Microbiology.
Although the U.S. Surgeon General claimed in the mid-1970s that infectious diseases had been conquered, the ensuing years have brought us Legionnaires disease; the toxic shock syndrome; an awareness of Lyme disease; an outbreak of hantavirus infection; and, of course, HIV. The discovery that peptic ulcer and gastric cancer are manifestations of Helicobacter pylori infection has led to an increasing search for the infectious nature of other "noninfectious" diseases, such as atherosclerosis. And this is just in the United States. Worldwide, one can add dengue, cholera, diphtheria, and a score of other infectious diseases that seem to be new or have long been relegated to the realm of the clinical "zebras."
Infectious diseases remain the leading cause of death and morbidity on our planet. Yet we have lived in populations large enough to sustain epidemic disease for less than 10 000 years. Of course, war, famine, poverty, and neglect, which are so prevalent in human populations, are always the harbinger of infection and disease. We also need to consider that our domestication of animals a scant 8000 years ago (a blink of the eye in evolutionary time) had a profound effect on the evolution of human disease. Measles is derived from canine distemper, mycobacteria came from ungulates, diphtheria came from water buffalo, and so on. Humans have always been confronted with "emerging infectious disease."
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The Enemy Is Us
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The cartoon character Pogo, invented by Walt Kelly, once announced to
his companions that "I have met the enemy and he is us." I
believe that many of what we refer to as emerging diseases can be
traced to subtle differences in human behavior and technology rather
than to changes in bacterial populations. For example, the
aerosolization of water in western society, ranging from the
widespread use of showers instead of baths to the spraying of
produce in supermarkets to air conditioning, has probably played a
significant role in the emergence of Legionnaires disease and Mycobacterium
avium infection in both normal and immunocompromised hosts. Legionella
pneumophila is found widely in nature as an infectious agent of
predatory protozoans. Introduction of this bacillus, which is often
found in potable water, as part of an aerosol into the alveolus of
the lung lets the microorganisms find a new niche in the macrophage
instead of in its usual hosts, Acanthamoeba or Hartmannella
species. Women in western society asked for extra-absorbent tampons
to help them achieve more social freedom. They were unwittingly
given a product that helped select for a new "emerging"
disease, the toxic shock syndrome. Food poisoning by Escherichia
coli O157, Campylobacter species, and Salmonella
species arises more often from food technology and food distribution
networks than from any fundamental change in the virulence of the
bacteria in question. I do not mean to turn our attention away from
the pathogenic traits of the disease-causing microbes, but, upon
reflection, it does seem true that technology and social behavior
have played a significant role in providing pathogenic microbes with
new venues for their wares.
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What Is a Pathogen, Anyway?
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In medicine, we view pathogens as any microorganism capable of
causing disease; the emphasis is on the disease, not the microorganism.
From the microbial standpoint, however, being pathogenic is simply a
strategy for survival. Humans are home to myriad living creatures,
from the mites that inhabit our eyebrows to the seething cauldron of
more than 600 species of bacteria that inhabit our large bowels. We
are a veritable microbial garden. Most of these microorganisms are
not only innocuous but play useful, if unseen, roles in our lives.
They protect us against the few harmful microorganisms that we
encounter each day; they provide us with some vitamins and
nutrients; and they help us digest our food. We have harbored them
for so long in our evolution that they are even a necessary part
of the developmental pathways required for the maturation of our
intestinal mucosa and our innate local immune systems.
Most of our microbes are commensal, that is, "they eat from the same table." Commensal or transient microbes can be opportunistic pathogens of humans; they can cause disease if one or more of the usual defense mechanisms are breached by accident, medical intent, or an underlying metabolic or even infectious disorder. The nosocomial infection is no stranger to the readers of this journal. Nevertheless, it is the small group of microorganisms that cause infection and overt disease in seemingly normal persons that are the "professional" pathogens. Many microorganisms, such as the typhoid bacillus, the gonococcus, the tubercle bacillus, and the treponema of syphilis, are adapted exclusively to humans; others, such as Salmonella typhimurium, can cause disease in both humans and other animals, birds, and even reptiles. One distinct difference among commensal microbes, opportunist microbes, and pathogens is that pathogens have evolved the genetic ability to breach the cellular and anatomic barriers that ordinarily restrict other microorganisms. Thus, pathogens have the ability to damage cells in order to forcefully gain access to a new, unique niche that provides less competition from other microorganisms, as well as a new source of nutrients. Pathogens have also learned to circumvent, exploit, subvert, or avoid our normal cellular mechanisms for their own selfish need to multiply at our expense.
We are beginning to understand how microbes made the transition from harmless commensal to potentially fatal infectious agents. An undercurrent of mobile genetic elements flows from microbe to microbe under the right conditions. It does not happen often, but when it does, it can be a cataclysmic genetic event that forever changes the microbe from a harmless companion into a potentially treacherous invader. All of the pathogenic strains of E. coli, be they the cause of urinary tract infection, the cause of traveler's diarrhea, or the enterohemorrhagic O157 organisms, evolved because they inherited a large block of DNA from some other microbial entity that provided a new strategy for survival and replication outside of the colon, which is inhabited by their nonpathogenic brethren.
In each case, a new pathogen was born. The lesson is simple: One genetic moment under the selective pressure of survival can be sufficient to cause a major change in the host-parasite relationship. History is full of examples of the sudden appearance of life-threatening diseases, such as plague, syphilis, and cholera. The more recent examples of emerging infectious diseases, cited above, are but a continuum of this same process. This continuum may seem more compelling because it occurs now rather than in the past, but the same forces are in play, intensified by larger populations, increased travel, and our destruction of some of nature's balancing forces. For example, the deluge of antibiotics in medicine and agriculture has an extraordinary effect on microbial communities of the soil, our indigenous microbial flora, and the indigenous microbial flora of our plants and animals. It may be one of the most important evolutionary influences on the microbes of our planet since the collision between earth and a heavenly body that did in the dinosaurs.
We can plan, argue, and talk about emerging infections, but the plain fact of the matter is that we are dealing with the fundamental biology of the most numerous living creatures with whom we share the planet. It would be wrong to underestimate them or to overestimate our capacity to control them. Remember that life on our planet cannot exist without microorganisms and that we are destined, in the end, to be consumed by them. It is certainly true that we have conquered smallpox, and that polio and measles are but a matter of time, but any infectious disease textbook now lists many more potential infectious agents than it did a scant 20 years ago. We are not helpless, of course, but we also can no longer take it for granted that the conquest of the world's leading killer of humans, infectious diseases, will happen all that soon.
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Author and Article Information
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Stanford University School of Medicine; Stanford, CA 94305-5124
Requests for Reprints: Stanley Falkow, PhD, Department of Microbiology
and Immunology, Fairchild, Room D039, Stanford University School of Medicine,
299 Campus Drive, Stanford, CA 94305-5124.
MICROBE
INFECTION.HTM