9. Patogenesis Infeksi Bakteri

8/9/2019 9. Patogenesis Infeksi Bakteri

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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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9. Patogenesis Infeksi Bakteri