1 Microbes as parasites
A number of important and distinctive biologic characteristics must be taken into account when considering any organism in relation to infectious disease. One of these is the way in which the organism is constructed, particularly the way in which genetic material and other cellular components are organized.
Viruses are not cells – they do have genetic material (DNA or RNA) but lack cell membranes, cytoplasm and the machinery for synthesizing macromolecules, depending instead upon host cells for this process. Conventional viruses have their genetic material packed in capsules. The agents (prions) which cause diseases such as Creutzfeldt–Jakob disease (CJD), variant CJD and kuru in humans, scrapie and bovine spongiform encephalopathy (BSE) in animals, appear to lack nucleic acid and consist only of infectious proteinaceous particles.
All other organisms have a cellular organization, their bodies being made up of single cells (most ‘microbes’) or of many cells. Each cell has genetic material (DNA) and cytoplasm with synthetic machinery, and is bounded by a cell membrane.
There are many differences between the two major divisions: prokaryotes and eukaryotes, of cellular organisms (Fig. 1.1). These include the following.
Another important difference between prokaryotes and the majority of eukaryotes is that the cell membrane (plasma membrane) of prokaryotes is covered by a thick protective cell wall. In Gram-positive bacteria, this wall, made of peptidoglycan, forms the external surface of the cell, while in Gram-negative bacteria there is an additional outer layer rich in lipopolysaccharides. These layers play an important role in protecting the cell against the immune system and chemotherapeutic agents, and in stimulating certain pathologic responses. They also confer antigenicity.
There is an important distinction between microparasites and macroparasites that overrides their differences in size. Microparasites (viruses, bacteria, protozoa, fungi) replicate within the host and can, theoretically, multiply to produce a very large number of progeny, thereby causing an overwhelming infection. In contrast, macroparasites (worms, arthropods), even those that are microscopic, do not have this ability: one infectious stage matures into one reproducing stage, and, in most cases, the resulting progeny leave the host to continue the cycle. The level of infection is therefore determined by the numbers of organisms that enter the body. This distinction between microparasites and macroparasites has important clinical and epidemiologic implications.
The boundary between microparasites and macroparasites is not always clear. The progeny of some macroparasites do remain within the host, and infections can lead to the build-up of overwhelming numbers, particularly in immune-suppressed patients. The roundworms Trichinella, Strongyloides stercoralis and some filarial nematodes, and Sarcoptes scabiei (the itch mite), are examples of this type of parasite.
Absolute size has other biologically significant implications for the host–pathogen relationship, which cut across the divisions between micro- and macroparasites. Perhaps the most important of these is the relative size of a pathogen and its host’s cells. Organisms that are small enough can live inside cells and, by doing so, establish a biologic relationship with the host that is quite different from that of an extracellular organism – one that influences both disease and control.
The basis of all host–pathogen relationships is the exploitation by one organism (the pathogen) of the environment provided by another (the host). The nature and degree of exploitation varies from relationship to relationship, but the pathogen’s primary requirement is a supply of metabolic materials from the host, whether provided in the form of nutrients or (as in the case of viruses) in the form of nuclear synthetic machinery. The reliance of viruses upon host synthetic machinery requires an obligatory intracellular habit: viruses must live within host cells. Some other groups of pathogens (Chlamydia, Rickettsia) also live only within cells. In the remaining groups of pathogens, different species have adopted either the intracellular or the extracellular habit, or, in a few cases, both. Intracellular microparasites other than viruses take their metabolic requirements directly from the pool of nutrients available in the cell itself, whereas extracellular organisms take theirs from the nutrients present in tissue fluids, or, occasionally, by feeding directly on host cells (e.g. Entamoeba histolytica, the organism associated with amoebic dysentery). Macroparasites are almost always extracellular (though Trichinella is intracellular), and many feed by ingesting and digesting host cells; others can take up nutrients directly from tissue fluids or intestinal contents.
As will be discussed in greater detail in Chapter 13, the intracellular pathogens pose problems for the host that are quite different from those posed by extracellular organisms. Pathogens that live within cells are largely protected against many of the host’s defence mechanisms while they remain there, particularly against the action of specific antibodies. Control of these infections depends therefore on the activities of intracellular killing mechanisms, short-range mediators or cytotoxic agents, although the latter may destroy both the pathogen and the host cell, leading to tissue damage. This problem, of targeting activity against the pathogen when it lives within a vulnerable cell, also arises when using drugs or antibiotics, as it is difficult to achieve selective action against the pathogen while leaving the host cell intact. Even more problematic is the fact that many intracellular pathogens live inside the very cells responsible for the host’s immune and inflammatory mechanisms and therefore depress the host’s defensive abilities. For example, a variety of viral, bacterial and protozoal pathogens live inside macrophages, and several viruses (including HIV) are specific for lymphocytes.
Intracellular life has many advantages for the pathogen. It provides access to the host’s nutrient supply and its genetic machinery and allows escape from host surveillance and antimicrobial defences. However, no organism can be wholly intracellular at all times: if it is to replicate successfully, transmission must occur between the host’s cells, and this inevitably involves some exposure to the extracellular environment. As far as the host is concerned, this extracellular phase in the development of the pathogen provides an opportunity to control infection through defence mechanisms such as phagocytosis, antibody and complement. However, transmission between cells can involve destruction of the initially infected cell and so contribute to tissue damage and general host pathology.