Principles of Microbial Pathogenicity and Epidemiology

PRINCIPLES OF MICROBIAL PATHOGENICITY AND EPIDEMIOLOGY

Introduction

Microorganisms are ubiquitous, and most of them are free-living and derive their nutrition from inert organic and inorganic materials. The association of humans with such microorganisms is generally harmonious, as the majority of those encountered are benign and, indeed, are often vital to commerce, health and a balanced ecosystem. The ability of bacteria and fungi to establish infections of plants, animals and humans varies considerably. Some are rarely, if ever, isolated from infected tissues, while opportunist pathogens (e.g. Pseudomonas aeruginosa or Staphylococcus epidermidis) can establish themselves only in compromised individuals. Only a few species of bacteria may be regarded as obligate pathogens, for which animals or plants are the only reservoirs for their existence (e.g. Neisseria gonorrhoeae, Mycobacterium tuberculosis and Treponema pallidum). Viruses, on the other hand, must parasitize host cells in order to replicate and are therefore inevitably associated with disease. Even among the viruses and obligate bacterial pathogens the degree of virulence varies, in that some (particularly the bacteria) are able to coexist with the host without causing overt disease (e.g. Staph. aureus), while others will always cause some detriment to the host (e.g. rabies virus). Organisms such as these invariably produce their effects, directly or indirectly, by actively growing on or in the host tissues.

Other groups of microorganisms may cause disease through ingestion of substances (toxins) produced during microbial growth on foods (e.g. Clostridium botulinum, botulism; Bacillus cereus, vomiting). In this case, the organisms themselves do not have to proliferate in the host for the effects of the toxin to be manifested.

Animals and plants constantly interact with bacteria present within their environment. For an infection to develop, such microorganisms must remain associated with host tissues and increase their numbers more rapidly than they can be either eliminated or killed. This balance relates to the ability of the bacterium to mobilize nutrients and multiply in the face of innate defences and a developing immune response by the now compromised host.

The greater the number of bacterial cells associated with the initial challenge to the host, the greater will be the chance of disease. If the pathogen does not arrive at its ‘portal of entry’ to the body or directly at its target tissues in sufficient number, then an infection will not ensue. The minimum number of viable microorganisms that is required to cause infection and thereby disease is called the minimum infective number (MIN). The MIN varies markedly between the various pathogens and is also affected by the general health and immune status of the individual host. The course of an infection can be considered as a sequence of separate events that includes initial contact with the pathogen, its consolidation and spread between and within organs and its eventual elimination (Figure 7.1). Growth and consolidation of the microorganisms at the portal of entry commonly involves the formation of a microcolony (biofilm), Biofilms and microcolonies are collections of microorganisms that are attached to surfaces and enveloped within exopolymers (biofilm matrix) composed of polysaccharides, glycoproteins and/or proteins. Growth within the matrix not only protects the pathogens against opsonization and phagocytosis by the host but also modulates their micro-environment and reduces the effectiveness of many antibiotics. The localized high cell densities present within the biofilm communities also initiate production, by the colonizing organism, of extracellular virulence factors such as toxins, proteases and siderophores (low molecular weight ligands responsible for the solubilization and transport of iron (III) in microbial cells). These are associated with a phenomenon termed quorum sensing and help the pathogen to combat the host’s innate defences and also promote the acquisition of nutrients.