PATHOGENESIS
OF
BACTERIAL INFECTION
PATHOGENICITY TOXIGENICITY
VIRULENCE
Eri Dian
Introduction of Normal Flora
1.
A diverse microbial flora =>
Human body Area: the skin and mucous membranes
Time: shortly after birth until death
Number: 1014 bacteria
2.
Normal flora may:
a. Aid the host
b. Harm the host (in sometimes)
c. Exist as commensals (no effect to the host)
3.
Viruses and parasites => NOT normal microbial flora
Most investigators consider that they are not commensals and do not aid the
host.
Significance of Normal Flora
Normal flora may aid the host in several ways:
Aid in digestion of food
Help the development of mucosa immunity
Protect the host from colonization with pathogenic microbes
Normal Flora competing with Invading
Pathogens
Adopted from Samuel Baron Medical Microbiology
Normal flora may act as opportunistic
pathogens
Especially in hosts rendered susceptible by:
1. Immuno-suppression (AIDS & SCID)
2. Radiation therapy & Chemotherapy
3. Perforated mucous membranes
4. Rheumatic heart diseaseetc.
Sites of human body that the normal flora
microbes colonize
Respiratory tract and head
outer ear, eye, mouth, oropharynx, nasopharynx
Sterile sites: sinuses, middle ear, brain, lower respiratory tract
(trachea, bronchiole, lung)
Gastrointestinal tract
esophagus, stomach, small intestine, large intestine
Genitourinary system
anterior urethra, vagina
Sterile sites: bladder, cervix, uterus
Skin
Medically important members of the normal
flora
Location
Important organis
Skin
Stapylococcus epidermidis
Nose
Stapylococcus aureus
Mouth
Streptococcus viridans
Dental plaque
Streptococcus mutants
Ginggival cervices
Bacteroides,Fusobacterium,
Streptococci,Actinomycetes
Throat
Streptococcus viridans
Colon
Bacteroides fragilis,Escherichia coli
Vagina
Lactobacillus,E.coli, Streptococci group
B
Urethra
S.epidermidis,Corynebacterium
(diphteroids),various Streptococci
,various gram-negative rods,E.g., E.coli
Distribution of Normal Flora in Human
Body
Adopted from Samuel Baron Medical Microbiology
Factors Influencing Normal Flora
1. Local Environment (pH, temperature, redox
potential, O2, H2O, and nutrient levels).
2. Diet
3. Age
4. Health condition (immune activity)
5. Antibiotics,..etc
The pathogenesis of bacterial infection includes the
initiation of the infectious process and the
mechanisms leading to the development of signs
and symptoms of bacterial disease.
The outcome of the interaction between bacteria
and host is determined by characteristics that favour
establishment of the bacteria within the host and
their ability to damage the host as they are opposed
by host defense mechanisms.
Among the characterics of bacteria are
adherence to host cells, invasiveness,
toxigenity, and ability to evade the hosts
immune system.
If the bacteria or immunological reactions
injure the host sufficiently, disease
becomes apparent.
Pathogenesis
of bacterial infection
Humans and animals have abundant normal microflora.
Most bacteria do not produce disease but achieve a
balance with the host that ensures the survival, growth,
and propagation of both the bacteria and the host.
Sometimes bacteria that are clearly pathogens (e.g.
Salmonella typhi) are present, but infection remains
latent or subclinical and the host is a "carrier" of the
bacteria.
Guidelines for Establishing the causes of Infectious Diseases
Koch's Postulates
1.
Microorganisms are isolated from dead animals
2.
Microorganisms are grown in pure culture
2b. Microorganisms are identified
3.
Microorganisms are injected into healthy animals
4.
Disease is reproduced in second animal
5.
Microorganisms are grown in pure culture
5b. Identification of identical microorganism.
Figure 14.3 - Overview
Figure 14.3, steps 12
Figure 14.3, steps 34
Figure 14.3, step 5
Exceptions to Kochs Postulates
Microorganisms that are unable to be cultured on
artificial media
(example: Treponema pallidum,Mycobacterium
leprae)
2 or more organism work in synergy to cause a
disease.
Symptoms and diseases can be causes by any one of
several microbes.
In another example, Neisseria gonorrhoeae (gonorrhea),
there is no animal model of infection even though the
bacteria can readily be cultivated in vitro.
The hosts immune responses should be considered when an
organism is being investigated as the possible cause of a
disease.
Thus, development of a rise in specific antibody during
recovery from disease is an important adjunct to Kochs
postulates.
Establishment of Infection
In order to cause disease pathogen must follow a
series of steps
Gain entrance to host
Adherence
Colonization and Number of Invading Microbes
Avoid Host Defenses
Cause host damage
Portals of entry
1. Mucus membranes
Respiratory tract
Gastrointestinal tract
Genitourinary tract
Placenta
2. Skin
3. Parenteral route
Bite, puncture, injection,
wound
The infectious process
Infection indicates multiplication of microorganisms.
Prior to multiplication, bacteria (in case of bacterial
infection) must enter and establish themselves within
the host.
The most frequent portals of entry are the respiratory
(mouth and nose), gastrointestinal, and urogenital
tracts. Abnormal areas of mucous membranes and skin
(e.g. cuts, burns) are also frequent sites of entry.
The infectious process
Once in the body, bacteria must attach or adhere to host cells,
usually epithelial cells.
After the bacteria have established a primary site of infection,
they multiply and spread.
Infection can spread directly through tissues or via the
lymphatic system to bloodstream. Bloodstream infection
(bacteremia) can be transient or persistent. Bacteremia allows
bacteria to spread widely in the body and permits them to
reach tissues particularly suitable for their multiplication.
The infectious process
As an example of the infectious process, Streptococcus pneumoniae can
be cultured from the nasopharynx of 5-40% of healthy people.
Occasionally, Streptococcus pneumoniae strains from the nasopharynx are
aspirated into the lungs. Infection develops in the terminal air space of
the lungs in persons who do not have protective antibodies against that
type of Streptococcus pneumoniae. Multiplication of Streptococcus
pneumoniae strains and resultant inflammation lead to pneumonia. The
strains then enter the lymphatics of the lung and move to the
bloodstream. Between 10% and 20% of persons with Streptococcus
pneumoniae pneumonia have bacteremia at the time the diagnosis of
pneumonia is made. Once bacteremia occurs, Streptococcus pneumoniae
strains can spread to their preferred secondary sites of infection (e.g.
cerebrospinal fluid, heart valves, joint spaces). The major resulting
complications of Streptococcus pneumoniae pneumonia include
meningitis, endocarditis and septic arthritis.
Basic terms frequently used in describing aspects
of pathogenesis:
Infection:
Multiplication of an infectious agent within the
body.
Multiplication of the bacteria that are part of normal
flora of gastrointestinal tract, skin, etc, is generally
not considered an infection.
On the other hand, multiplication of pathogenic
bacteria (e.g. Salmonella species), even if the person
is asymptomatic, is deemed an infection.
Basic terms frequently used in describing aspects
of pathogenesis:
Pathogenicity:
The ability of an infectious agent to cause disease.
Virulence:
The quantitative ability of an agent to cause disease.
Virulent agents cause disease when introduced into the host in
small numbers.
Virulence involves invasiveness and toxigenicity.
Basic terms frequently used in describing
aspects of pathogenesis:
Toxigenicity:
The ability of a microorganism to produce a toxin
that contributes to the development of disease.
Invasion:
The process whereby bacteria, parasites, fungi
and viruses enter the host cells or tissues and
spread in the body.
Basic terms frequently used in describing
aspects of pathogenesis:
Pathogen:
A microorganism capable of causing disease.
Non-pathogen:
A microorganism that does not cause disease. It may be part of the
normal flora.
Opportunistic pathogen:
An agent capable of causing disease only when the hosts resistance
is impaired (e.g. the patient is immunocompromised).
An agent capable of causing disease only when spread from the site
with normal bacterial microflora to the sterile tissue or organ.
Bacterial virulence factors
Many factors determine the virulence of
bacteria, or their ability to cause
infection and disease.
Toxins
Toxins produced by bacteria are
generally classified into two groups:
exotoxins
endotoxins
Exotoxins versus Endotoxins
Exotoxin
Enzymes
Many species of bacteria produce enzymes that are not intrinsically
toxic but play important role in the infectious process.
Collagenase:
degrades collagen, the major protein of fibrous connective
tissue, and promotes spread of infection in tissue.
Coagulase:
Staphylococccus aureus produce coagulase, which works in
conjuction with serum factors to coagulate plasma. Coagulase
contributes to the formation of fibrin walls around
staphylococcal lesions, which helps them persist in tissues.
Enzymes
Hyaluronidases:
enzymes that hydrolyze hyaluronic acid, a constituent of the ground
substance of connective tissue. They are produced by many bacteria
(e.g. staphylococci, streptococci and anaerobes) and aid in their
spread through tissues.
Streptokinase:
many hemolytic streptococci produce streptokinase (fibrinolysin),
substance that activates a proteolytic enzyme of plasma. This enzyme,
also called fibrinolysin, is then able to dissolve coagulated plasma and
probably aids in the spread of streptococci through tissues.
Streptokinase is used in treatment of acute myocardial infarction to
dissolve fibrin clots.
enzymes lyse cells, form or dissolve clots, and dissolve
materials in tissue.
Coagulases
Kinases
Hyaluronidase
Dissolves hyaluronic acid
Collagenase
Enzymes
Hemolysins and leukocidins:
Many bacteria produce substances that are
cytolysins - they dissolve red blood cells
(hemolysins) or kill tissue cells or leukocytes
(leukocidins).
Streptolysin O, for example, is produced by group A
streptococci and is letal for mice and hemolytic for
red blood cells from many animals.
Antiphagocytic factors
Many bacterial pathogens are rapidly killed once they are
ingested by polymorphonuclear cells or macrophages.
Some pathogens evade phagocytosis or leukocyte
microbidical mechanisms by adsorbing normal host
componets to their surfaces.
For example, Streptococcus pneumoniae have surface factors
that impede phagocytosis e.g. and many other bacteria have
polysaccharide capsules.
Adherence factors
Once bacteria enter the body of the host, they must
adhere to cells of a tissue surface. If they do not
adhere, they would be swept away by mucus and
other fluids that bathe the tissue surface.
Adherence (which is only one step in the infectious
process) is followed by development of microcolonies
and subsequent complex steps in the pathogenesis of
infection.
Adherence factors
The interactions between bacteria and tissue
cell surfaces in the adhesion process are
complex.
Several factors play important role:
surface hydrophobicity
binding molecules on bacteria and host cell
receptor interaction
and other
Adherence
Attachment between of microbe to host tissue requires:
Adhesins or Ligands: Surface molecules on pathogen that bind
specifically to host cell surface molecules. May be located on
glycocalyx, fimbriae, viral capsid, or other surface structure.
Ex: Protein A (Staphylococcus aureus)
Protein M (Streptococcus pyogenes)
Receptors: Surface molecules on host tissues to which pathogen
adhesins bind.
Cell Wall Components
M protein: Found on cell surface and fimbriae of Streptococcus
pyogenes. Mediates attachment and helps resist phagocytosis.
Waxes: In cell wall of Mycobacterium tuberculosis helps resist
digestion after phagocytosis.
Adherence (adhesion)
Critical Step
Bacteria use adhesins (ligands)
Viruses has surface attachment proteins
Binding to host cells receptors is highly specific
Definitions...........
Opportunistic infection
An infection caused by microorganisms that
are commonly found in the hosts environment
This term is often used to refer to infections
caused by organisms in the normal flora
Acute vs. Persistent Infections
Acute - a natural infection that usually is
rapid and self limiting
Influenza virus,rhinovirus,rotavirus
Persistent - a natural infection that can be
long term, slow,latent ,transforming
HIV, Herpes simplex virus
Acute infection vs. chronic
infection
Acute Infection
An infection characterized by sudden onset,
rapid progression, and often with severe
symptoms
Chronic Infection
An infection characterized by delayed onset
and slow progression
Mode of Transmission
Direct Mechanisms of Disease Transmission
Directly From Person to Person
Examples:
Direct Skin Contact
Airborne (Aerosols)
Indirect Mechanisms of Disease Transmission
Examples:
Food & Waterborne Transmission
Fomites
Animal Vectors
An animal (nonhuman) that can transmit an infectious agent to
humans
