The capsule of Streptococcus pneumoniae is a pathogenicity determinant
because without it the organism does not usually cause
disease. Some capsular types cause more serious disease i.e. they
are more virulent (Streptococcus pneumoniae, other Gram-positive cocci and the alpha-haemolytic streptococci
). The term parasite is often used to
describe protozoan and metazoan organisms, but this is confusing
as these organisms may be either pathogens or commensals.
Types of pathogen
Obligate pathogens are always associated with disease (e.g.
Treponema pallidum and HIV). Conditional pathogens may cause
disease if certain conditions are met. For example, Bacteroides
fragilis is a normal commensal of the gut but if it invades the
peritoneal cavity, it will cause severe infection. Opportunistic
pathogens usually cause infection when the host defences are compromised.
For example, Pneumocystis jiroveci usually causes lung
infection only in a host who has severely compromised T-cell
Mechanisms of pathogenicity
The process of infection has several stages.
Access to a vulnerable host - transmission
Organisms are transmitted by various means but most are restricted
to a particular route (Sources and transmission of infection
). Strains may develop epidemic
potential by developing adaptation to an environment that either
favours transmission or better survival in that environment. For
example, most respiratory pathogens induce coughing, which
facilitates their spread by the creation of respiratory droplets. The
vomiting and diarrhoea associated with organisms that are spread
by the faecal-oral route increase contamination of the environment
and the risk of new infection.
Attachment to the host
Microorganisms must attach themselves to host tissues to colonize
them and each organism has a different strategy. The distribution
of the receptors to which a particular organism can bind will define
the organs that it will infect, as in the following examples.
- Neisseria gonorrhoeae adheres to the genital mucosa using
- Influenza virus attaches by its haemagglutinin antigen. This
accounts for both species-specific pathogenesis (the ability of
certain strains to cause disease in a particular species, such as avian
or porcine strains) and intraspecies variation in affinity and susceptibility
- Bacterial biofilms aid colonization of indwelling prosthetic
devices, such as catheters and the respiratory tract. Some
strains of staphylococci have genes that mediate attachment to
plastics and to the biological molecules that coat intravascular
- Mucosal destruction may expose a variety of host molecules
such as fibronectin, vibronectin and collagen to which invading
organisms can bind.
Some bacteria have mechanisms that help them get close to the
mammalian epithelium. For example, Vibrio cholerae excretes a
mucinase to help it reach the enterocyte. Microorganisms have a
variety of strategies that allow them to cross mucosal barriers or
different types of cell membrane.
The ability to move in order to locate new sources of food or in
response to chemotactic signals potentially enhances pathogenicity.
V. cholerae is motile by virtue of its flagellum - non-motile
mutants are less virulent.
To survive in the human host, pathogens must overcome the host
Damaging the host
- Respiratory bacteria secrete an IgA protease that degrades host
- Staphylococcus aureus expresses protein A, which binds host
immunoglobulin, preventing opsonization and complement
- S. pneumoniae has a polysaccharide capsule, which inhibits
phagocytosis by polymorphonuclear neutrophils.
- Toxoplasma gondii, Leishmania donovani and Mycobacterium
tuberculosis are adapted to survive within macrophages using different
- The lipopolysaccharide (LPS) of Gram-negative organisms
makes them resistant to the effect of complement.
- Trypanosoma alter surface antigens to evade antibodies.
Endotoxins stimulate macrophages to produce cytokines such as
interleukin-1 (IL-1) and tumour necrosis factor (TNF) that cause
fever and shock.
Bacterial exotoxins can cause local or distant damage. They are
usually proteins and may have a subunit structure.
- Cholera toxin B subunit binds to the epithelial cell and the A
subunit activates adenyl cyclase, which results in sodium and chloride
efflux from the cell, thus causing diarrhoea.
- Staphylococcal enterotoxins act as superantigens, causing nonspecific
activation of T cells that have compatible variable region
structure, which results in intense cytokine production leading to
fever, shock, gastrointestinal disturbance and rash.
- Diphtheria toxin and Pseudomonas aeruginosa exotoxin A stop
protein production by blocking elongation of proteins.
- Clostridial toxins interfere with neurological or neuromuscular
signalling causing, for example, tetanus and botulism.
In many cases antibody to the toxin ameliorates the physiological
effects of the disease and is therefore protective (see