cause death in 50 % of the inoculated animals in a defined
time interval. ID50 is the number of pathogens required to
cause disease in 50 % of animals after inoculation and incubation for a well-defined time period. ID50 for humans is less
than 1,000 for Salmonella enterica Typhi but is between 1 and
10 for Mycobacterium tuberculosis or Francisella tularensis
and 1 for the amoeba Naegleria fowleri. The ID50 seems
higher for opportunistic pathogens, although the measurement
is difficult for these pathogens because of the specificities of
opportunistic infections.
15.3.1 Entry Routes
15.3.1.1 Skin and Conjunctival Routes
The skin barrier is a good protection, but a simple wound
can lead to an infection. Skin and conjunctival infections (e.g.,
P. aeruginosa keratitis) are often benign but can become
severe if the wounds are deeply infected and if primary
pathogens such as Staphylococcus aureus or opportunist
ones such as Nocardia are involved. S. aureus can be found
in recreative waters while being shed by healthy swimmers.
Nocardia (part of the Actinobacteria) are of environmental
origin (Fig. 15.3) and can be found in soils and waters.
15.3.1.2 Respiratory Route
In this case, inhalation of contaminated aerosols can occur
naturally or through artificial mechanical ventilators, implying invasive or noninvasive procedures. Contamination of
the inhaled aerosols can be due to infected individuals or
environmental sources such as showers, air conditioners, and
cooling towers (legionellosis). Certain agricultural practices
such as spreading of composts and manure or a close proximity with wastewater treatment plants or combined sewer
overflows can lead to human infections through inhalation
of contaminated aerosolized particles.
15.3.1.3 Oral Route
This is the most important route of entry of microorganisms
into the human body. Most food products harbor a microflora,
and ingestion of food contaminated by infectious agents can
rapidly lead to an infection. Children and the elderly but also
immunocompromised individuals are the most sensitive to
such exposures, e.g., the recent E. coli O104:H4 outbreaks.
15.3.2 Colonization Processes
15.3.2.1 Adhesion Properties
Most microbial infections imply colonization through the
main entry points of the human body and affect or involve
the mucous membranes of the respiratory, intestinal, or
urinary tracts and most particularly interactions with the
epithelial cells. The pathogen must be able to recognize
and adhere to molecules at the surface of host cells which
are often proteins. These molecules generally serve specific
function in the host organism. For example, the AIDS virus
(or HIV) can adhere to T cells that have CD4 receptors* on
their surface and whose major function is the immune
system (white blood cells). After infection, this role in
host defense is inhibited and the host becomes vulnerable
to other pathogens. Furthermore, some pathogenic bacteria
can use pili (fimbriae) to adhere to mucosal cells. Some
will develop biofilms after an intense production of
exopolysaccharides.
15.3.2.2 Growth Within Host Tissues
Some microorganisms are able to produce a number of
extracellular enzymes or toxins among which we can
mention the hyaluronidases (which facilitate the spread of
bacteria in tissues), fibrinolysins (to dissolve fibrin clots
produced by the host), proteases (collagenase, elastase),
nucleases and pilases (increases invasiveness), hemolysins
(which attack the red blood cell membranes), and
leukocidins (which can lyse white blood cells and reduce
host resistance).
15.3.2.3 The Ability to Enter and Survive
Within Eukaryotic Cells
Some pathogens can enter and survive within nonphagocytic eukaryotic cells such as epithelial cells of
mucosal surfaces or endothelial cells of blood vessels.
15.3.2.4 The Ability to Escape the Immune
Defenses of the Host
Some microorganisms, including bacteria, have evolved
mechanisms to circumvent host defenses. The most important ones relate to the production of antiphagocytic factors
such as capsules* and surface proteins but also the ability to
survive and reproduce within macrophages (internalized
Legionella pneumophila being able to withstand acidity,
proteases, and free radicals from the phagolysosome), resistance to serum bactericidal activity, the development of
siderophores* to chelate iron from the host proteins, the
development of IgA proteases, the variation of surface
antigens, and molecular mimicry.
15.3.3 Toxigenic Activities
Beyond extracellular toxic factors that promote invasiveness,
bacteria can produce toxins that are responsible for symptoms
or even some syndromes associated with infection. Toxins act
as poisons which are lethal to the host and are sometimes used
to penetrate tissues. For example, Clostridium perfringens can
produce a collagenase which degrades collagen tissue and
allows penetration by the infectious agent inside the tissue.
There are two types of toxins: (1) endotoxins which are
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