What is a Pathogen?

WHAT IS A PATHOGEN?

In medicine, we define a pathogen as any microorganism capable of causing disease. The emphasis is on disease, not the microorganism. However, from the microbial standpoint, being pathogenic is a strategy for survival and simply one more remarkable example of the extraordinary diversity of the microbial world. Humans, including physicians, proba-bly spend too little time reflecting on the fact that we are home to a myriad of other living creatures. From mouth to anus, from head to toe, every millimeter of our cells that is exposed to the outside world has a rich biological diversity. From the mites that inhabit the eyebrows of many of us to the seething cauldron of over 600 species of bacteria that inhabit our large bowel, we are a veritable garden of microorganisms. Most of these mi-croorganisms are not only innocuous but play a useful, if unseen, role. Not only do they provide us with protection against the few harmful microorganisms that we encounter each day, but they also give us some vitamins and nutrients and help digest our food. We have harbored them so long in our evolution that they are even a necessary part of the de-velopmental pathways required for the maturation of our intestinal mucosa and our innate local immune system.

Most human microbes are commensal; that is, they eat from the same table that we do. These microbes are constant companions and often depend on humans for their exis-tence. Although humans do not appear to be absolutely dependent on microbes for life (at least the cultivatable ones we know), we exist more comfortably with microbes than with-out them. We also encounter transient microbes, which are just passing through or on us, so to speak. Some commensal transient species may be opportunistic pathogens. These  organisms can cause disease only if one or more of the usual defense mechanisms hu-mans have evolved to restrict microorganisms from their usually sterile internal organs and tissue are breached by accident, by intent (eg, surgery), or by an underlying meta-bolic or an infectious disorder (eg, AIDS). Nevertheless, a small group of microorganisms often causes infection and overt disease in seemingly normal individuals. These are the primary pathogens such as the common cold virus, the mumps virus, the typhoid bacil-lus, gonococcus, the tubercle bacillus, and the treponema of syphilis. Each organism is adapted exclusively to humans; other pathogens such as Salmonella typhimurium, a com-mon cause of human food poisoning, can cause disease both in humans and other ani-mals, birds, and even reptiles.

What is the difference between a commensal, an opportunist, and a primary pathogen? All of these organisms can cause disease under the proper circumstances. One distinction to make between an opportunistic pathogen and a primary pathogen is on the basis of the essentiality of the host for the long-term survival of a microbe. Long-term survival in a primary pathogen is absolutely dependent on its ability to replicate and to be transmitted in a particular host; however, this is not necessarily the case for a number of the opportunistic pathogens that infect humans. The major distinction that emerges is that primary pathogens have evolved the genetic ability to breach human cellular and anatomic barriers that ordinarily restrict or destroy commensal and transient microorgan-isms. Thus, pathogens can inherently cause damage to cells to gain access by force to a new unique niche that provides them with less competition from other microorganisms, as well as a ready new source of nutrients. For microorganisms that inhabit mammals as an essential component of their survival tactic, success can be measured by the capacity to multiply sufficiently to be maintained or be transmitted to a new susceptible host. This is true for commensal and pathogen alike. However, if the pathogen gains a new niche free of competition and rich in nutrients, it also faces a more hostile environment de-signed by evolution to restrict microbial entry and, indeed, to destroy any intruders that dare to enter these protected regions. Thus, pathogens have not only acquired the capacity to breach cellular barriers, they also have, by necessity, learned to circumvent, exploit, subvert, and even manipulate our normal cellular mechanisms to their own selfish need to multiply at our expense.

The strategy for survival of a pathogen requires infection (persistence, usually by multiplication on or within another living organism). Disease (ie, the overt clinical signs and symptoms of damage that occur in a host as a result of its interaction with an infec-tious agent) may not be an inevitable outcome of the host-parasite interaction. Rather, the requirement for a microbial infection is sufficient multiplication by the pathogen to se-cure its establishment within the host by transient or long-term colonization or to bring about its successful transmission to a new susceptible host. Thus, many (or most) com-mon infections are inapparent and asymptomatic. Symptoms of disease can reflect part of the microbe’s strategy for survival within the host. For example, coughing promotes the transmission of the tubercle bacillus and influenza virus, and diarrhea spreads enteric viruses, protozoa, and bacteria.

Physicians often use the terms virulent and pathogenic interchangeably. Originally, virulence was used as a comparison of pathogenicity in the quantitative sense, and thisuse of the term is still preferred. For example, the bacterial species Haemophilus influen-zae is a common inhabitant of the upper respiratory tract of humans. Members of thisspecies regularly cause middle-ear infection and sinusitis in children and bronchitis in smokers, but one variety of H. influenzae (those with capsule type b) can cause systemic disease (meningitis and epiglottitis). All H. influenzae are pathogenic, but H. influenzae type b is more virulent.