Transmission

Most infections are acquired by transmission from external sources; i.e. they are exogenous in origin. Others are caused by members of the normal flora behaving as opportunist pathogens; i.e. they are endogenous in origin. Transmission can be by:

There are four important portals (or gates) of entry of pathogens (Table 5.1):

Table 5.1 Portals of entry of some common pathogens

Adherence to host surfaces

Adherence is the first step in infection. Unless organisms have the ability to stick or adhere to host surfaces, they will be unable to cause infection. Some bacteria and fungi have specialized structures or produce substances that facilitate their attachment to the surface of human cells or prostheses (e.g. dentures, artificial heart valves), thereby enhancing their ability to colonize and cause disease. These adherence mechanisms are critical for organisms that attach to mucous membranes; mutants that lack these mechanisms are often non-pathogenic (e.g. the hair-like pili of Neisseria gonorrhoeae and Escherichia coli mediate their attachment to the urinary tract epithelium; the extracellular polysaccharides of Streptococcus mutans help it adhere to enamel surfaces).

Biofilm formation

Once the organisms adhere to a host surface they usually tend to aggregate and form intelligent communities of cells called biofilms. A biofilm is defined as an aggregate of interactive bacteria attached to a solid surface (such as a denture prosthesis or an intravenous catheter) or to each other, encased in an extracellular polysaccharide matrix. Up to 65% of human infections are thought to be associated with microbial biofilms. Dental plaque on solid enamel surfaces is a classic example of a biofilm. As biofilms are ubiquitous in nature and form on hulls of ships, warm water pipes, dental unit water systems and so on, their study has rapidly evolved during the past few decades, leading to many discoveries on communal behaviour of microbes.

As mentioned, biofilms are intelligent communities. Structurally, they are not flat and compressed but comprise a complex architecture with towers and mushroom or dome-shaped structures with water channels that permit transport of metabolites and nutrients (Figs 5.1–5.3). Bacteria in biofilms maintain the population level by constantly secreting low levels of chemicals called quorum-sensing molecules (e.g. homoserine lactone), which tend to repulse incoming bacteria or activate the communal bacteria to seek new abodes. Further, specific gene activation may lead to production of virulence factors or reduction in metabolic activity (especially those living deep within the matrix).

Fig. 5.1 The ultrastructure of (A) an early biofilm on a dental appliance showing the deposition of coccal and bacillary forms; (B) a mature dental plaque biofilm on a dental appliance showing the advancing edge and the complex architecture.

(Courtesy of Dr Bernard Low.)

Fig. 5.2 A schematic diagram depicting the various developmental stages of a biofilm from the initial adherent phase (left) of the organisms to gradual maturation and subsequent fully developed polymicrobial biofilm (extreme right). EPS, extracellular polysaccharide.

Fig. 5.3 A mature Candida albicans biofilm showing water channels (arrows) that mediate metabolite and nutrition transfer to and from the biofilm (inset: magnified channel architecture).

It is now known that infections associated with biofilms are difficult to eradicate as sessile organisms in biofilms exhibit higher resistance to antimicrobials than their free-living or planktonic counterparts. The reasons for this appear to be (Fig. 5.4):

Fig. 5.4 Postulated mechanisms of antibiotic resistance in biofilms: the attachment surface is shown at the bottom and the aqueous phase containing the antibiotic at the top.

(Modified from Stewart and Costerton Lancet 2001; 358; 135–138 with permission.)

Some examples of important recalcitrant human infections mediated by biofilms, difficult to manage by antimicrobials alone, include Pseudomonas aeruginosa infections of the respiratory tract in cystic fibrosis patients, Staphylococcus aureus infections in central venous catheters, chronic candidal infections of HIV-infected individuals and chronic periodontal infections due to dental plaque.

Invasiveness

Invasiveness of bacteria plays a critical role in pathogenesis; this property is dependent upon secreted bacterial enzymes. A few examples are:

Other factors also contribute to invasiveness by interfering with the host defence mechanisms, especially phagocytosis:

Table 5.2 Examples of surface virulence factors that interfere with host defences

Bacterial infection may lead to two categories of inflammation: pyogenic (pus-producing) and granulomatous (granuloma-forming).