Introduction to Bacteria and Bacterial Diseases

Classification of Bacteria

Bacteria have been classified according to phenotype, including size, shape, staining properties, and biochemical properties, since the beginning of microbiology. In recent years classification has been dominated by genotype, especially relying on conserved molecules, such as 16S ribosomal RNA. Although there is a considerable degree of overlap between phenotype and genotype, as would be expected, dichotomies occur. In the future, taxonomy, understanding of pathogenesis, and diagnostics will be increasingly based on genotype and gene expression. Even in resource-limited settings, rapid genotypic identification of drug-resistant M. tuberculosis is close at hand. Proteins expressed under a given condition can be determined by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, which generates proteomic mass patterns or fingerprints. As a method for identification of microorganisms, this is rapidly being integrated into the routine analytic pipeline of clinical microbiology laboratories. More advanced “proteotyping” will provide strain-level characterization, including virulence and antibiotic resistance factor expression. Thus physicians and other students of infectious diseases must broaden their knowledge of molecular biology and taxonomy. As bacteriology advances in its differentiation of genera and species, as subspecies diversity is increasingly appreciated, as variation within individual hosts is better understood, and as the evolution of pathogens is better outlined, a grounding in evolutionary biology and ecology also will become more critical. The recent National Institutes of Health Human Microbiome Project already has provided a new scientific basis for the biomedical community toward understanding strain and species variation among the indigenous organisms in human hosts. Over time, this information will be translated into clinical advances in prevention, diagnosis, and treatment of infectious diseases; studies of the human microbiome are already suggesting bacterial roles in diseases that were not previously suspected to have a microbial cause.

Variation in Bacterial Infections

Because all organs of the body are subject to bacterial infection, a recitation of these sites would be exhaustive and thus not useful. However, at the least, bacterial infections may be considered as varying in cause, mechanisms, and time frame. Infections may be caused by gram-positive or gram-negative bacilli or cocci; these were the first recognized bacterial agents of disease. However, this simple taxonomy does not fully account for other causative bacterial agents, including Mycobacterium species, treponemes, mycoplasmas, rickettsiae, chlamydiae, and actinomyces, all of which are Eubacteria. Each of these types of organisms has particular stereotypic features that characterize its interactions with hosts, but exceptions and variations abound. In recent years Archaea, a widespread and ancient group of prokaryotes, most closely resembling bacteria, has been isolated from human specimens ; the extent to which they play roles in human diseases is not yet known.

The mechanisms whereby bacteria cause disease are quite varied ( Table 193.1 ). There is no universal mechanism or principle; the causative organism need not even be present in the human body. For example, food poisoning is commonly caused by the ingestion of preformed toxin produced by Clostridium botulinum or Staphylococcus aureus when they are growing in food, not in the host. The scope of bacterial infections includes interactions across time frames that vary from minutes to decades, or longer ( Table 193.2 ). The descendants of the organisms that we each acquire from our mother as a newborn can be the cause of our death in old age (e.g., caused by a perforated diverticulum) to carry the argument to the farthest extreme. Each bacterial infection is unique and reflects the underlying virulence properties of the bacteria and the predisposition of the host. For example, commensals or generally nonpathogenic environmental organisms can cause devastating disease in certain hosts because of genetic inborn errors ; acquired immunodeficiencies from diverse causes, such as human immunodeficiency virus, autoantibodies, or immunomodulatory drugs; or from anatomic defects, such as perforated viscera, indwelling lines, or traumatic injuries. This complexity increases the difficulty in grasping the underlying concepts but also makes the practice of infectious diseases so intellectually satisfying.