5: Pathogenesis of microbial disease

Chapter 5 Pathogenesis of microbial disease

If a microorganism is capable of causing disease, it is called a pathogen. Fortunately, only a minority of the vast multitude of microorganisms in nature are pathogenic. Whereas some organisms are highly virulent and cause disease in healthy individuals, even with a small inoculum, others cause disease only in compromised individuals when their defences are weak. The latter are called opportunistic organisms, as they take the opportunity offered by reduced host defences to cause disease. These opportunists are frequently members of the body’s normal flora.

General aspects of infection

Pathogenesis of bacterial disease

Determinants of bacterial pathogenicity

Bacterial pathogenicity is a vast subject. The following is a brief outline of the ways and means by which bacteria cause disease. The major steps are transmission, adherence to host surfaces, invasiveness and toxigenicity.

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

Portal of entry Pathogen Disease
Skin Clostridium tetani Tetanus
  Hepatitis B virus Hepatitis B
Respiratory tract Streptococcus pneumoniae Pneumonia
  Neisseria meningitidis Meningitis
  Haemophilus influenzae Meningitis
  Mycobacterium tuberculosis Tuberculosis
  Influenza virus Influenza
  Rhinovirus Common cold
  Epstein–Barr virus Infectious mononucleosis
Gastrointestinal tract Shigella dysenteriae Dysentery
  Salmonella typhi Typhoid fever
  Vibrio cholerae Cholera
  Hepatitis A virus Infectious hepatitis
  Poliovirus Poliomyelitis
Genital tract Neisseria gonorrhoeae Gonorrhoea
  Treponema pallidum Syphilis
  Human immunodeficiency virus (HIV) Acquired immune deficiency syndrome (AIDS)
  Candida albicans (fungus) Vaginitis

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 5.15.3). 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).

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):

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

Organism Virulence factor Used in vaccine
Bacteria    
Streptococcus pneumoniae Polysaccharide capsule Yes
Streptococcus pyogenes M protein No
Staphylococcus aureus Protein A No
Neisseria meningitidis Polysaccharide capsule Yes
Haemophilus influenzae Polysaccharide capsule Yes
Klebsiella pneumoniae Polysaccharide capsule No
Escherichia coli Protein pili No
Salmonella typhi Polysaccharide capsule No
Mycobacterium tuberculosis Mycolic acid cell wall No
Fungi    
Cryptococcus neoformans Capsule No

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

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Jan 4, 2015 | Posted by in General Dentistry | Comments Off on 5: Pathogenesis of microbial disease
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