Pathogenesis of bacterial infection
A microorganism capable of causing disease are known as
pathogen,and the ability to causes disease is
calledpathogenicity and the extent of pathogenicity known
as a (Virulence).
The pathogenesis of bacterial infection means the steps or
mechanisms involved in the development of a disease.
The pathogenesis of bacterial infection includes initiation of
infectious process and the mechanisms that lead to the
development ofsigns (objective changes the physician can
observe & measure) andsymptoms(unobserved changes in
body functions) of disease.
Many infections caused by bacteria that are considered to be
pathogens are inapparent or asymptomatic, and the person
with this kind of infection called carrier.
STEPS IN THE PATHOGENESIS OF INFECTIOUS DISEASE
In general, the pathogenesis of infectious disease often follows
this sequence:
1. Entry of the pathogen into the body by:
penetration of skin or mucous membranes by the
pathogen
Inoculation of the pathogen into body tissues by an
arthropod.
Inhalation (airborne disease).
Ingestion (the gastrointestinal tract).
Introduction of the pathogen into the genitourinary tract.
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Introduction of the pathogen into the blood via blood
transfusion or intravenous drug abusers.
Sexual transmission also other port of microbial entry.
Many pathogens have preferred portals of entry that are
necessary for disease production.
If they gain entrance via another portal, disease may not occur.
Examples:
Salmonella typhi produces disease when swallowed
but not if rubbed on the skin.
Streptococci that are inhaled can cause pneumonia
but, if swallowed, generally do not produce disease.
2. Adherence (attachment) of the pathogen to the host
cells, usually epithelial cells. This attachment is
accomplished by means of surface molecules on the
pathogen called (adhesins or ligands),which is bind
specifically to complementary surface receptors on the
cells of certain host tissues ,adhesins may be located on
microbial surface structures such as pili, fambriae.
The majority of adhesins on bacteria are glycoproteins or
lipoproteins.The host receptors typically sugar such as
(mannose).
3. Colonization (multiplication) of the pathogen in one
location of the body, resulting in a localized infection (e.g., an
abscess), or it may multiply throughout the body (systemic
infection).
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4. Invasion /spread of the pathogen.Not all bacteria are
invasive. Invasive organisms attach and enter host cells
by a number of mechanisms:
I. Production of surface proteins called invasins that
rearrange host cell actin filaments.
II. Production of enzymes:
Collagenase which breaks down collagen in
connective tissue.
hyaluronidase which breakdown hyaluronic acid
that holds cells together (particularly connective
tissue cells).
Coagulase which converts fibrinogen to fibrin
producing a clot (may be protective against
phagocytes).
Kinases which can breakdown clots decreasing the
isolation of bacteria in clots (spreading effect).
DNAase , Lipase, Phospholipase, Proteases are
other enzymes cause tissue destruction .
5. Evasion of host defenses:
When the microorganism invades a body tissue, it will
face host phagocytes.
If invader is destroying by phagocytes, no further damage
is done to the host tissue.
6. Damage to host tissue.
If the pathogen overcomes the host’s defense, damaging
to the host cells will occur in four basic ways:
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i. By using the host’s nutrients specifically iron which
is required for bacterial growth.
In order to get free iron, pathogenic bacteria
produce siderophores proteins
Which binding to host iron transport proteins and
take the iron into the bacterium.
ii. By direct host tissue damage as the pathogens use the
host cell for nutrient, produce waste products, multiply
in host cells causing cell rupture, and pathogenic spread
to other host tissue in greater numbers.
iii. By producing toxins which are byproducts of bacterial
growth that are poisonous to host cells; transported via
blood & lymph causing serious and sometimes fatal
effects. They produced by certain microorganisms and
the ability of microorganisms to produce toxins is known
as Toxigenicity.
In many cases, the toxin is completely responsible for
causing the characteristic symptoms of the disease (e.g.
toxins in food poisoning).
Basically, there are two major types, exotoxins and
endotoxins.
1) Exotoxins:
Proteins, produced inside some bacteria as part of their
growth and metabolism. Generally, they are released while
the bacterium is actively growing but may also be released
when the organism die.
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Produced by both gram positive and gram negative
bacteria and include cytolytic enzymes and dimeric toxins
with A& B subunits.
The genes for most exotoxins are carried on bacterial
plasmids or bacteriophages.
Exotoxins are typically soluble in body fluids and can easily
diffuse into the blood where they are rapidly transported
systemically.
The A subunit is the active enzymatic component.
The B subunit is the binding component.
When the A-B toxin is released from the bacterium, the B
subunit binds to a surface receptor on the host cell.
Following binding, the toxin is transported across the
plasma membrane where the two subunits separate. The A
subunit then exerts its enzymatic activity.
Superantigens
Are special types of exotoxin that can bind to the outside of the T
cell receptor and a class II major histocompatibility complex
receptor (MHC II) on antigen-presenting cells.
This binding is not specific for a particular T cell and can result in
production of large quantities of cytokines including interleukin
1, 2 and tumor necrosis factor TNF, leading to systemic
inflammatory responses.
Examples:Staphylococcal toxic shock syndrome toxin, enterotoxins
and erythrogenic toxins.
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2) Endotoxin
Is a part of the outer portion of the gram negative cell wall.Also
called lipopolysaccharide or LPS.
The actual toxic component of endotoxin is lipid A.
Endotoxin is released as gram negative bacteria lyse (although
some endotoxin is also released during replication).
Unlike exotoxin, endotoxins are relatively resistant to heat.
At higher concentrations, endotoxin can induce what is known as
gram negative shock, septic shock or endotoxic shock.
Due to activation of the complement pathway with the
production of C3a, C4aand C5a.
These components are referred to as anaphylatoxins and
they cause smooth muscle contraction, histamine release
from mast cells, and enhanced vascular permeability.
Along with inflammatory cytokines can lead to fluid loss from
the vasculature and result in hypotension and shock.
Fever also results as IL-1 and TNF stimulate the
hypothalamus to adjust body temperature.
Disseminated intravascular coagulation (DIC) can also result
from activation of the clotting mechanism.
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MECHANISMS OF EVADING HOST DEFENSES:
Capsules – the chemical nature of the capsule appears to
prevent phagocytic cells from adhering to the organism.
Capsules are often polysaccharide in nature but may be amino
acid (Bacillus anthracis).
Cell wall components such as M protein in Streptococcus
pyogenes, mediates attachment and inhibits phagocytosis.
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Intracellular growth, such as Neisseria gonorrhoeae,
Mycobacterium tuberculosis
Antigenic variation occurs when the organism has the genetic
ability to produce different structural compositions for a
particular bacterial structure which is recognized as an antigen
by the immune system.
