Part I
Characteristics of Microorganisms
Chapter 1
The Microbial World
Key Facts
- Microorganisms are all around us in enormous numbers and are present both on and within our bodies. Some, termed pathogens, cause disease; others are beneficial and are of commercial importance but the vast majority are harmless.
- Infectious diseases can be caused by agents which are not living microorganisms: prions are simply ‘rogue’ protein molecules, and viruses usually consist of nucleic acid and protein but have no cellular structure.
- Bacteria represent the simplest living cells. Most of those of pharmaceutical interest can be grown easily in the lab.
- Fungi and protozoa are more complex than bacteria and most of them can exhibit sexual reproduction.
- Relatively few fungi are pathogenic; most are important as contaminants and spoilage organisms in manufactured medicines.
- Protozoa are only of pharmaceutical interest as pathogens; they are not spoilage organisms.
1.1 Microorganisms Around Us
Microorganisms are present in almost every location and environment on earth. They are in the air, soil and water, on all plants and animals and in such extreme environments as Antarctic ice and rocks 3 km below the earth's surface where the temperature is 60° C or more. Besides growing at extremes of temperature and pH, many bacteria survive and grow in the absence of oxygen; for these bacteria, described as anaerobes, oxygen is toxic. Microorganisms are present, too, in huge numbers and variety. The bacteria in the average human gut are estimated to comprise about 500 different species, and their total number, approximately 1014 (one hundred trillion), is about 10 times the number of human cells in the body and more than 10 000 times the human population of the earth. It is impossible to obtain precise data on the relative numbers of harmless and disease-causing (pathogenic) organisms for two main reasons: because new species are being identified all the time, and because of the difficulty of deciding what is harmless and what is not. Organisms that present no threat to a healthy individual might be pathogenic for a person with impaired immunity. Nevertheless, despite the extensive media attention on bioterrorism organisms and the so-called hospital ‘superbugs’, the harmless bacteria, together with those that are actually beneficial, grossly outnumber the pathogens; one estimate is by a ratio of more than 200 000 to 1.
1.2 The Benefits of, and Problems with, Microorganisms
Microorganisms can be essential, passively beneficial or positively useful (Table 1.1). They are essential for the maintenance of life on earth as part of the carbon and nitrogen cycles, for example; without them, dead animals and plants would not decompose and the fertility of soils would fall. Their passive benefits include the protection afforded by probiotic (‘friendly’) bacteria, which compete with disease-causing species for nutrients and attachment sites on body tissue; they also limit opportunities for harmful bacteria to establish infections in the body by producing antimicrobial chemicals. The practical uses of microorganisms include their long-established rôles in the brewing, dairy and food sectors, and their applications in the pharmaceutical industry, which have multiplied enormously in recent years. Bacteria and fungi have been used since the 1940s to make antibiotics, and since the 1950s in the production of contraceptive- and cortico-steroids, but it was the 1980s, a decade which brought major advances in genetic engineering, which saw bacteria used for the manufacture of insulin, human growth hormone, vaccines and many other biotechnology products (see Chapter 20).
Table 1.1 Examples of benefits, uses and problems associated with microorganisms.
- Essential role in carbon and nitrogen cycles
- In brewing, dairy and food industries
- In the manufacture of several industrial solvents and other chemicals
- As an insecticide
- Chemical detoxification
- In oil extraction
- ‘Biological’ detergents
| - In the manufacture of: antibiotics, steroids, vaccines and many biotechnology products
- Used in assays to measure antibiotic concentrations
- As biological indicators of sterilization (Chapter 19)
- Used in tests to detect metabolic disorders and mutagenicity
| - Cause infections
- Even harmless species may transmit antibiotic resistance
- Even dead bacteria may cause fever (endotoxins)
- Contaminate and spoil nonsterile medicines
- Cause noninfectious diseases, e.g. gastric ulcers and some cancers
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Despite their applications in industry and the increasing recognition of their benefits, it is still the case that the main pharmaceutical interest in microorganisms is in killing them or, at least, restricting their contamination and spoilage of medicines. The reasons for this interest are listed in Table 1.1, and although the first of these – that microorganisms cause infection – is quite obvious, the other problems that microorganisms pose are less well recognized. It is tempting to suppose both that harmless bacteria are irrelevant and that dead bacteria do no harm. Unfortunately, neither supposition is correct: harmless bacteria can carry genes responsible for antibiotic resistance, which they may transfer to disease-causing species, and components of the cell walls of dead bacteria (termed endotoxins) cause fever if they enter the blood stream. Consequently, in order to avoid the risk of fever from residual endotoxins when an injection is administered, it is necessary to ensure that the injection, which must be sterile (free of living organisms) anyway, has not been contaminated with high levels of bacteria during its manufacture. However, it is not only sterile medicines where microorganisms can present a problem: the great majority of medicines are not sterile, and the risk here is that the living organisms they do contain may damage the product, either by altering its physical stability or by breaking down the active ingredient.
1.3 The Different Types of Microorganisms
Living organisms are made up of cells of two types: prokaryotic and eukaryotic. Bacteria used to be considered as the only category of prokaryotic cells, but in 1990 a second group, the archaea, were recognized as having equal status to bacteria. Archaea tend to live in inhospitible conditions (high temperatures, extremes of pH or salinity for example) and often possess unusual modes of metabolism, but because no pathogenic archaea have yet been discovered this group will not be considered further. All other organisms are eukaryotic, so the major groups of microorganisms (fungi, protozoa and algae), as well as parasitic worms and mites, and all plants and animals up to and including humans, are eukaryotes. Viruses do not have a cellular structure and so some scientists do not even regard them as living but merely mixtures of complex chemicals; nevertheless, they are indisputably agents of infection and for that reason are usually considered as part of the micro...