Pathogenic organisms

After the German physician Koch had formulated his postulates about pathogenic organisms in 1891, numerous practical problems arose in meeting these for each presumptive causative agent. For many parasitic diseases these postulates have still not been met today. In particular, in vitro cultivation raises problems (fastidious organisms, complex life-cycles in various hosts). This has resulted over the course of history in the separation of bacteriology (+ virology at a later date) on the one hand and parasitology on the other.

These postulates are:

1. The disease organism must be associated with the disease.

2. The organism must be isolated and then grown in pure culture.

3. The cultured organism must cause the disease after inoculation into a sensitive host.

4. The organism isolated from the second host must be identical to the first.

"Common" bacteria: e.g. those causing plague, cholera, typhoid fever, bacterial meningitis. Antibiotics often are first choice in treatment. On the basis of the structure of the outermost layer of the bacteria, organisms can be classified into Gram-positive and Gram-negative. These can be distinguished by means of a particular staining method (Gram stain). Bacteria can be rod-shaped or round (bacilli and cocci, respectively). Some are spiral (e.g. spirochaetes) or comma-shaped (e.g. vibrios). Mycoplasma are the smallest free-living bacteria. They are not detectable by Gram stain. Chlamydiae and rickettsiae are also difficult to detect under the light microscope because of their small dimensions (often smaller than the optical resolution of the instrument).

The Danish physician Hans Christian Gram in 1884 developed a staining method which still bears his name today. Bacteria in suspension are fixed on a glass slide by heating for a short time. Two substances (crystal violet and lugol [containing iodine]) are added successively and then react to form a coloured complex in each bacterium. When the carrier glass is subsequently rinsed with an alcohol or acetone, bacteria with a thick cell wall retain the stain, while those with a thin cell wall lose it. A second counterstain is then applied with a weaker red stain (safranin or dilute carbol fuchsin). [The latter should not be confused with strong carbol fuchsin used in Ziehl’s stain]. Gram staining thus reveals differences in cell wall structure.

Gram-positive bacteria have a cell wall that consists of a very thick peptidoglycan layer. It forms a thick latticework around the bacterium. The peptidoglycan layer in Gram-negative bacteria is only 1 to 2 molecules thick. Peptidoglycan is a polymer of a disaccharide (2 different sugars, N-acetylglucosamine and D-acetyl muramic acid). The sugar chains are bound to one another by oligopeptide bridges. Peptidoglycan synthesis is impaired for example by beta-lactam antibiotics. In Gram-negative bacteria, the thin peptidoglycan layer is surrounded by an outer membrane that consists of lipopolysaccharides (containing endotoxin). These are of great importance in pathogenicity.

Mycobacteria: e.g. Tuberculosis, leprosy, Buruli ulcer. Treatment of these diseases requires a different set of antibiotics. Special staining of the wax-like capsule is necessary to detect the organisms (Ziehl-Neelsen stain).

Chlamydiae: e.g. Trachoma, psittacosis, lymphogranuloma venereum. Some cause pulmonary inflammation, others congenital infections and eye inflammations. They possess an incomplete metabolism and are obliged to live intracellularly. They are susceptible to some specific antibiotics.

Rickettsiae: e.g. typhus. Very small, obligate intracellular bacteria named after their discoverer, Howard Ricketts. Tetracyclines constitute the basic treatment.

Fungi: Moulds (mycelium formation) and yeasts (no mycelium, sometimes pseudohyphae). A mycelium is a cluster of branched filaments formed by the organisms. Some organisms live preferentially on the skin (dermatophytes) and some on mucous membranes (Candida). Others cause deep infections e.g. cryptococcal meningitis. Specific therapy is indicated. Some fungi produce toxic substances. When these find their way into food, health problems can follow, e.g. ergotism (Claviceps purpurea) and aflatoxicosis (Aspergillus niger). Allergic problems are common.

Viruses: e.g. yellow fever, dengue, rabies, polio, herpes, HIV. These organisms cannot reproduce independently and do not possess their own metabolism. They are obliged to reproduce intracellularly. Sometimes treatment with virostatics is indicated, but often only symptomatic therapy is possible.

Prions: e.g. kuru, Creutzfeldt-Jacob disease, bovine spongiform encephalopathy (BSE, “mad cow disease”). In the first half of the 20th century kuru was a major neurological problem with a fatal outcome. This disease only occurred in cannibals of the Fore tribe in Papua New Guinea. Our knowledge of this and related diseases is clearly inadequate. The current hypothesis is that the disease is caused by a modified form of a normal protein. This modified protein possesses a well-defined three-dimensional configuration (tertiary structure). This form of the protein catalyses the conversion of other proteins from the one steric, non-pathogenic form of the protein to the other pathogenic form. As a result, the protein acts like an infectious agent. The change of form, however, can also occur as a result of a genetic mutation in the DNA coding for the protein.

Protozoa: unicellular organisms that contain a cell nucleus surrounded by a nuclear membrane: eukaryotes (as opposed to prokaryotes - bacteria). There are specific treatments for each disease.

e.g. Sleeping sickness, malaria, amoebiasis, leishmaniasis, giardiasis, toxoplasmosis.

Metazoa: Multicellular eukaryotic organisms, diverging considerably in size and taxonomic relationship. E.g. whip worms, bilharziasis, scabies, lung flukes.

Category: Medicine Notes