The next stage
of infection is invasion that is the penetration of the epithelium
to generate pathogenicity. At the point of entry, usually at small
breaks or lesions in the skin or mucosal surfaces, growth is often
established in the submucosa. Growth can also be established on
intact mucosal surfaces, especially if the normal flora is altered
or eliminated. Pathogen growth may also be established at sites
distant from the original point of entry. Access to distant, usually
interior, sites occurs through the blood or lymphatic system.
If a pathogen gains access to tissues by adhesion and invasion, it
must then multiply, a process called colonization. Colonization
requires that the pathogen bind to specific tissue surface receptors
and overcome any non-specific or immune host defenses. The initial
inoculum is rarely sufficient to cause damage. A pathogen must grow
within host tissues in order to produce disease. If a pathogen is to
grow, it must find appropriate nutrients and environmental
conditions in the host. Temperature, pH and reduction potential are
environmental factors that affect pathogen growth, but the
availability of microbial nutrients in host tissues is most
important. Not all nutrients may be plentiful in different regions.
Soluble nutrients such as sugars, amino acids and organic acids may
often be in short supply and organisms able to utilize complex
nutrient sources such as glycogen may be favored. Trace elements may
also be in short supply and can influence the establishment of a
pathogen.
For example,
iron is thought to have a strong influence on microbial growth.
Specific iron binding proteins called transferrin and lactoferrin
exist in human cells and transfer iron through the body. Such is the
affinity of these proteins for iron, that microbial iron deficiency
may be common and administration of a soluble iron salt may greatly
increase the virulence of some pathogens. Many bacteria produce
iron-chelating compounds known as siderophores, which help them to
obtain iron from the environment. Some iron chelators isolated from
pathogenic bacteria are so efficient that they can actually remove
iron from host iron binding proteins. For example, a siderophore
called aerobactin, produced by certain strains of E. coli and
encoded by the Col V plasmid, readily removes iron bound to
transferring.
After initial entry, the organism often remains localized and
multiplies, producing a small focus of infection such as a boil,
carbuncle or pimple. For example, these commonly arise from
Staphylococcus infections of the skin. Alternatively, the organism
may pass through the lymphatic vessels and be deposited in lymph
nodes. If an organism reaches the blood, it will be distributed to
distal parts of the body, usually concentrating in the liver or
spleen. Spread of the pathogen through the blood and lymph systems
can result in generalized (systemic) infection of the body, with the
organism growing in a variety of tissues. If extensive bacterial
growth in tissues occurs, some of the organisms may be shed into the
bloodstream, a condition known as bacteremia.
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