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PATHOGENESIS
OF
BACTERIAL INFECTION
PATHOGENICITY TOXIGENICITY
VIRULENCE
Eri Dian
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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 thehost.
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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
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Normal Flora competing with Invading
Pathogens
Adopted from Samuel Baron “Medical Microbiology”
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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 disease…etc.
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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
Sites of human body that the normal flora
microbes colonize
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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
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Adopted from Samuel Baron “Medical Microbiology”
Distribution of Normal Flora in Human
Body
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1. Local Environment (pH, temperature, redox
potential, O2, H2O, and nutrient levels…).
2. Diet
3. Age
4. Health condition (immune activity…)
5. Antibiotics,…..etc
Factors Influencing Normal Flora
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• The pathogenesis of bacterial infection includes theinitiation of the infectious process and themechanisms leading to the development of signsand symptoms of bacterial disease.
• The outcome of the interaction between bacteria
and host is determined by characteristics that favourestablishment of the bacteria within the host andtheir ability to damage the host as they are opposedby host defense mechanisms.
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• Among the characterics of bacteria are
adherence to host cells, invasiveness,toxigenity, and ability to evade the host´simmune system.
• If the bacteria or immunological reactionsinjure the host sufficiently, diseasebecomes apparent.
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Pathogenesisof bacterial infection
• Humans and animals have abundant normal microflora.
• Most bacteria do not produce disease but achieve abalance 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 thebacteria.
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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.
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Figure 14.3 - Overview
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Figure 14.3, steps 1 –2
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Figure 14.3, steps 3 –4
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Figure 14.3, step 5
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Exceptions to Koch’s Postulates
• Microorganisms that are unable to be cultured onartificial media
– (example: Treponema pallidum,Mycobacteriumleprae)
• 2 or more organism work in synergy to cause adisease.
• Symptoms and diseases can be causes by any one of
several microbes.
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• In another example, Neisseria gonorrhoeae (gonorrhea),
there is no animal model of infection even though thebacteria can readily be cultivated in vitro.
The host´s immune responses should be considered when an
organism is being investigated as the possible cause of adisease.
Thus, development of a rise in specific antibody during
recovery from disease is an important adjunct to Koch´s
postulates.
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Portals of entry
1. Mucus membranes
• Respiratory tract
• Gastrointestinal tract
• Genitourinary tract
• Placenta
2. Skin
3. Parenteral route• Bite, puncture, injection,
wound
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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 thelymphatic system to bloodstream. Bloodstream infection(bacteremia) can be transient or persistent. Bacteremia allowsbacteria to spread widely in the body and permits them toreach tissues particularly suitable for their multiplication.
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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 areaspirated into the lungs. Infection develops in the terminal air space ofthe lungs in persons who do not have protective antibodies against thattype 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 thebloodstream. Between 10% and 20% of persons with Streptococcus pneumoniae pneumonia have bacteremia at the time the diagnosis ofpneumonia 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 includemeningitis, endocarditis and septic arthritis.
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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 normalflora of gastrointestinal tract, skin, etc, is generallynot considered an infection.
– On the other hand, multiplication of pathogenicbacteria (e.g. Salmonella species), even if the personis asymptomatic, is deemed an infection.
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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.
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Basic terms frequently used in describing
aspects of pathogenesis:
• Toxigenicity :
– The ability of a microorganism to produce a toxinthat contributes to the development of disease.
• Invasion:
– The process whereby bacteria, parasites, fungi
and viruses enter the host cells or tissues andspread in the body.
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Basic terms frequently used in describingaspects 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 host´s resistance
is impaired (e.g. the patient is immunocompromised).
– An agent capable of causing disease only when spread from the sitewith normal bacterial microflora to the sterile tissue or organ.
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Bacterial virulence factors
• Many factors determine the virulence of
bacteria, or their ability to cause
infection and disease.
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Toxins
• Toxins produced by bacteria are
generally classified into two groups:
–exotoxins
–endotoxins
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Exotoxins versus Endotoxins
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Exotoxin
E
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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 connectivetissue, and promotes spread of infection in tissue.
• Coagulase:
– Staphylococccus aureus produce coagulase, which works inconjuction with serum factors to coagulate plasma. Coagulasecontributes to the formation of fibrin walls aroundstaphylococcal lesions, which helps them persist in tissues.
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Enzymes • Hyaluronidases:
–
enzymes that hydrolyze hyaluronic acid, a constituent of the groundsubstance of connective tissue. They are produced by many bacteria(e.g. staphylococci, streptococci and anaerobes) and aid in theirspread 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 andprobably aids in the spread of streptococci through tissues.Streptokinase is used in treatment of acute myocardial infarction to
dissolve fibrin clots.
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• enzymes lyse cells, form or dissolve clots, and dissolve
materials in tissue.
– Coagulases
– Kinases
– Hyaluronidase
• Dissolves hyaluronic acid
–
Collagenase
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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.
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Antiphagocytic factors• Many bacterial pathogens are rapidly killed once they are
ingested by polymorphonuclear cells or macrophages.
• Some pathogens evade phagocytosis or leukocytemicrobidical mechanisms by adsorbing normal host
componets to their surfaces.
• For example, Streptococcus pneumoniae have surface factorsthat impede phagocytosis e.g. and many other bacteria have
polysaccharide capsules.
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Adherence factors
• Once bacteria enter the body of the host, they mustadhere 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 ofinfection.
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Adherence
Attachment between of microbe to host tissue requires:
Adhesins or Ligands: Surface molecules on pathogen that bindspecifically to host cell surface molecules. May be located onglycocalyx, fimbriae, viral capsid, or other surface structure.
• Ex: Protein A (Staphylococcus aureus)
• Protein M (Streptococcus pyogenes)
Receptors: Surface molecules on host tissues to which pathogenadhesins 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 resistdigestion after phagocytosis.
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• Adherence (adhesion)
– Critical Step
–
Bacteria use adhesins (ligands) – Viruses has surface attachment proteins
– Binding to host cells receptors is highly specific
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Definitions...........
• Opportunistic infection
– An infection caused by microorganisms that
are commonly found in the host’s environment
This term is often used to refer to infectionscaused by organisms in the normal flora
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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
A i f i h i
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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 onsetand slow progression
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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
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