7313515 normal flora microbial pa tho genesis and host parasite relationship

7/30/2019 7313515 Normal Flora Microbial Pa Tho Genesis and Host Parasite Relationship

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Microbial Pathogenesisand Host-Parasite Relationships

Medical Microbiology

Normal Flora

For : www.esnips.com/web/m4mn

By: Mohammed M.M..Manaa

[email protected]


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Normal Flora

General aspects

Remember definition: organisms frequently found

on or within body of healthy individuals Most are bacteria, but some are viruses, fungi,

and protozoa

We do not carry all of them all of the time

Each person has individualized normal flora


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Normal Flora

Some are found only on body; others also

found in environment

Problem: some people have transient normalflora (pathogens)

Example: about 10% of population havemeningococcus or pneumococcus as normal

flora


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Importance

Depends on pathogen andon defenses ofhost:

Candida(yeast) causes pneumonia in peopleundergoing cancer chemotherapy

Pneumocystis carinii(common inhabitant of lung)causes pneumonia and death in AIDS patients


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Immune Stimulation

Antigenic stimulation by normal flora do

not have high antibody titers

Serve as defense mechanism even in lowconcentration

Bacterial stimulation leads to production of IgAthat is secreted through mucus membranes

Probably interfere with colonization of deeper tissues


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Immune Stimulation

Sometimes antibodies elicited by normal

flora cross-react with normal tissue:

Antibodies against ABO blood group substances: A - make B antibodies

B - make A antibodies

O - make antibodies against both

Why? Bacteria from intestinal flora contain Ag that cross-react with both A & B blood substances


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Immune Stimulation

Cross-reactivity does not normally cause

disease

Possible for antibodies cross-reactive to microbial Agto cause problem

Lupus erythematosusproduction of Ab against host DNA

Some evidence that Ag may be cross-reacting bacterial LPS

May cross-react with pathogen (meningococcus)


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Physical & Chemical Aspects

Keeps out invaders

Mechanisms:

Physical advantage of previous occupancy

Some produce bacteriocins or antibiotics

Relevance to lab work: E. coliK-12 cannot

compete with intestinal flora


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Antibiotic effects: wipes out normal flora

Both endogenous and exogenous organisms can

cause disease Infecting dose of Salmonelladecreases one million-fold

when mice given streptomycin

Patients treated with some potent antibiotics:

Suffer from diarrhea due to overgrowth of yeasts, andstaphylococci

Administration of clindmycin-Clostridium difficile(minormember of normal flora) causes pseudomembranous colitis


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Role in human nutrition and metabolism

E. coliand Bacteriodessynthesize vitamin K

Metabolism of key compounds involves excretion

from liver into intestine and their return to the liver


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Source of carcinogens

Large intestinal flora

Many potential carcinogens are only active after beingmodified

Some modifications are carried out by enzymes ofintestinal bacteria; example: cyclamate converted tobladder carcinogen (cyclohexamine) by bacterial

sulfatases Importance of carcinogen production not clear


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Ecology of Normal Flora

Use of germ-free animals

Immune systems not well developed

Have to be fed vitamins


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Ecology of Normal Flora

Parts of body colonized

Contain large numbers:

Skin

Respiratory tract (nose and oropharynx)

Digestive tract (mouth and large intestine)

Urinary tract (anterior parts of urethra)

Genital system (vagina) Most are strict anaerobes


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Strategies for StudyingMicrobial Pathogenesis

Medical Microbiology


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Identification of Pathogens

Traditional:associate disease withorganism


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Kochs Postulates

3 Pure culture inoculated into susceptibleanimal should produce disease

4 Same bacterium re-isolated in pure culture

from experimental animal


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Kochs Postulates

Some assumptions questioned in light of

more modern approaches and newinformation about host-parasite interaction


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Challenge to Postulate #2

Places considerable emphasis on culturing

organisms in pure culture

Some organisms have notbeen cultured inlaboratory media


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For example, Treponema pallidium,Mycobacterium lepraeclearly cause disease:

Antibiotics cause both symptoms and organisms

from tissues to disappear

Immune response in infected patients to surface

Ag of bacteria from infected tissue


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Implies all members of a bacterial species are

equally virulent and only a single species

causes disease

Different strains of species vary in virulence

Different strains can cause different diseases

Same symptoms caused by numerous organisms

Disease caused by multiple organisms


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Well known fact that cultivation of some

pathogens can lead to loss of virulencefactors


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Requires pathogen be reinoculated into an

animal and produces symptoms of disease

Some diseases dont affect animals, or cause

different symptoms from human form

Therefore, to be practical, Kochs Postulatesrequire animal models


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Identification of Pathogens

Molecular version


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Molecular Version

Emphasis shifted from identification of

pathogens to identification of virulence factors

Not completeagreement on requirements toprove a particular gene or product plays a role

in disease, but criteria widely accepted


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Molecular Version

1 Gene or product found in strains that cause

disease and not in avirulent bacteria

If gene found in organisms not known to

cause disease, gene should be mutated to lessactive or inactive form, or not expressed


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Molecular Version

2 Disrupting gene in virulent strain reduces or

eliminates its virulence

Introduction of cloned gene into avirulent strain

should make it virulent

Systems with multiple genes:

These other genes would also have to be modified

or introduced


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Molecular Version

3 Gene is expressed in bacteria inside host

sometime during disease process

4 Ab to gene product should be protective or incases where cell-mediated immunity

involved, gene product should elicitprotective immunity


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Identification without Culturing

Combine PCR:

Polymerase Chain Reaction with 16S r-RNA phylogeny

16S r-RNA found in all bacteria

Conserved (domain) and variable (particularorganism) sequences


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Sizable database and similarities in sequence

correspond well to evolutionary relationships

Sequence will either identify it as member of

known or unknown species


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PCR primers that recognize two conserved

regions of 16S rRNA flanking a variableregion are used to amplify and clone a DNA

segment from a clinical speciman

If amplified segment is obtained, indicatesbacteria present in speciman

It can be sequenced to identify bacterium


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Fluorescently labeled probe of sequence can

then visualize bacterium in clinical speciman

Rules out PCR amplification of contaminatingDNA from other sources

7313515 normal flora microbial pa tho genesis and host parasite relationship

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