bacteria

1. BACTERIAL PATHOGENESIS

2. Why we do not get ill?
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(i) the entire invading population is killed by phagocytic cells,
such as neutrophils, or circulating bacteriocidal compounds,
such as complement
(ii) the density of bacteria traversing the integument is
collectively too low to condition the tissue to allow their
population to grow or
(iii) the mutations or phase shifts required to get across the
mucosa or survive in the blood do not occur.
It is complex and strong stochastic

3. Introduction
Apathogen is a microorganism that is able to cause disease in a
plant, animal or insect.
Pathogenicity is the ability to produce disease in a host
organism.
Microbes express their pathogenicity by means of their
virulence, a term which refers to the degree of pathogenicity of the
microbe.
Determinants of virulence of a pathogen are any of its genetic
or biochemical or structural features that enable it to produce
disease in a host.
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4. The relationship between a host and a pathogen is dynamic, since
each modifies the activities and functions of the other.
The outcome of such a relationship depends on:
 the virulence of the pathogen and
the relative degree of resistance or susceptibility of the host,
mainly due to the effectiveness of the host defense mechanisms.
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Introduction

5. Animals and microbes
 Normal flora (beneficial or ignored):
 GI track, skin, upper respiratory track
 Virulent bacteria (actively cause disease):
 pathogenic islands
 Opportunistic bacteria (when host with underline problem):
 Pseudomonas aeruginosa: cystic fibrosis/ burn
 TB, Kaposi’s sarcoma (herpesvirus): AIDS
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6. Mechanisms of Bacterial Pathogenicity
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1. Invasiveness: the ability to invade tissues.
 encompasses mechanisms for
 colonization (adherence and initial multiplication),
 production of extracellular substances which facilitate
invasion (invasins) and
 ability to bypass or overcome host defense
mechanisms.

7. 2. Toxigenesis: ability to produce toxins.
Bacteria may produce two types of toxins:
i. exotoxins and
ii. endotoxins.
Mechanisms of Bacterial Pathogenicity
 Exotoxins are released from bacterial cells and may act at
tissue sites removed from the site of bacterial growth.
 Endotoxins are cell-associated substance. (classic sense,
endotoxin refers to the lipopolysaccharide component of the
outer membrane of Gram-negative bacteria).
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8.  Endotoxins may be released from growing bacterial cells
and cells that are lysed as a result of effective host defense
(e.g. lysozyme) or the activities of certain antibiotics (e.g.
penicillins and cephalosporins).
 Hence, bacterial toxins, both soluble and cell-associated,
may be transported by blood and lymph and cause cytotoxic
effects at tissue sites
 Some bacterial toxins may also act at the site of colonization
and play a role in invasion.
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Mechanisms of Bacterial Pathogenicity

9. Animals and microbes
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 Normal flora (beneficial or ignored):
 GI track, skin, upper respiratory track
 Virulent bacteria (actively cause disease):
 pathogenic islands
 Opportunistic bacteria (when host with underline problem):
 Pseudomonas aeruginosa: cystic fibrosis/ burn
 TB, Kaposi’s sarcoma (herpesvirus): AIDS

10. Robert Koch,1843-1910, Germany
Koch’s postulates:
1. suspected pathogen must be present
2. pathogen must be isolated and grown in pure culture
3. cultured pathogen must cause the disease
4. Same pathogen must be re-isolated from the subject
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Big person in microbiology

11. Bacterial pathogenesis
 Infection/entry
 Virulence factors
 Pathogenesis
 Escape of immune surveillance
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12. Infection/entry
 Ingestion (fecal-oral)
 Inhalation (respiratory)
 Trauma (e.g burn)
 Arthropod bite (zoonoses:
mosquito, flea, tick,
Tsetse fly)
 Sexual transmission
 Iatrogenic (needle stick,
blood transfusion)
 Maternal-neonatal
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13. Bacteria, virus, fungi
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 Ingestion: Salmonella, Shigella, Vibrio, Clostridium etc..
 Inhalation: Mycobacterium, Mycoplasma, Chlamydia etc..
 Trauma: Clostridium tetani
 Arthropod bite: Rickettsia, Y
ersinia pestis, etc.
 Sexual transmission: Neisseria gonorrboeae, HIV,
chlamydia, etc
 Needle stick: Staphylococcus, HIV, HBV
 Maternal-neonatal: HIV, HBV, Neisseria, etc.

14. Modes of infectious disease transmission
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Contact transmission
Direct contact (person-to-person): syphilis, gonorrhear, herpes
Indirect contact (fomites): enterovirus infection, measles
Droplet (less than 1 meter): whooping cough, strep throat
Vehicle transmission
Airborne: influenza, tuberculoses, chickenpox
Water-borne (fecal-oral infection): cholera, diarrhea
Food-borne: hepatitis, food poisoning, typhoid fever
Vector transmission
Biological vectors: malaria, plaque, yellow fever
Mechanical vectors: E. coli diarrhea, salmonellosis

15. Extracellular versus Intracellular Parasitism
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 Extracellular parasites
 destroyed when phagocytosed.
 damaging tissues as they remain outside cells.
 inducing the production of opsonizing antibodies, they
usually produce acute diseases of relatively short duration.
 Intracellular parasites
 can multiply within phagocytes.
 frequently cause chronic disease.

16. The environment in a cell
 Cytosol: pH=7
 Phagosome: pH=6
 Phagolysosome: pH=5
Adapted from: http://bio.winona.msus.edu/bates/Bio241/images/figure-04-13b.jpg
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17. Barrier systems
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Host cell
membrane
Taken up by
phagocyte
and resist killing
Inhibitory
molecule
Mycobacterium
Production
Of antibody
Degrade
antibody
IgA protease Streptococcus
Antimicrobial
cell-mediated
response
ActivateT cells
non-specifically
and
Productively
Superantigen Staphylococcus
Antimicrobial
immune
response
Vary presenting
microbial
antigen
Switch on
production of
different
antigens
Borrelia
Genetic
recombination
Streptococcus

18. Virulence factors
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Factors enhancing the ability of bacteria to cause disease
Example: Pseudomonas aeruginosa
 Adhesins: attachment
 Alginate production: mucoid layer
 ExotoxinA: inhibits host protein synthesis
 Exoenzyme S: interferes with phagocytic killing
 Elastolytic activity: degrades elastin
 Phospholipase C: damages tissue
 Pyocyanin: damages tissue by ROS
 Antibiotic resistance: complicates therapy

19. Pathogenic action of bacteria
 Tissue destruction: flesh-eating bacteria:
Clostridium perfrigens
 Obstruction: Cytic fibrosis
 Toxins: bacterial componentsthat directly
harm tissue or trigger disease symptoms
 Endotoxin: lipopolysaccharides
 Exotoxin:A-B toxins
 Immunopathogenesis
 Excess immune responses
 Autoimmunity
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20. 2. Endotoxins: heat stable
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21. A.S. HOZA
Endotoxin: lipopolysaccharide
IL-1
TNF
Pseudomonas aeruginosa
Fever
Disseminated intravascular coagulation
Septic shock
death

22. A.S. HOZA
Superantigens
PolyclonalT cell activation
Aberrant cytokines,
cell death
Specific T cell activation
Anti-microbes immunity
Antigen
/MHC-1
Secreted proteins
(exotoxins) that exhibit
highly potent lymphocyte-
transforming (mitogenic)
activity directed towards T
lymphocytes.

23. Known and suspected association of superantigens with
animal diseases
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Autoimmune diseases
Lyme disease
Multiple sclerosis
Acute diseases
Food poisoning:
Staph infections
Streptococal

24. EVASION STRATEGIES (1)
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Defence Microbial strategy Mechanism Example
Wash-out Bind to cell Adhesins Neisseria
Inhibit ciliary
activity
Ciliotoxic/
Ciliostatic
molecule
Bordetella
Streptococcus
Ingestion
and
killing by
phagocyte
Disrupt
Chemotaxis
cytotoxic
Leucocidins Staphylococcus
Inhibit
phagocytosis
Capsule Streptococcus
Inhibit lysosomal
fusion
Inhibitory
molecule
Mycobacterium
Multiply Unknown Listeria

25. EVASION STRATEGIES (2)
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Defence Microbial strategy Mechanism Example
Restrict Fe-
Lactoferrin
Transferrin
Compete Siderophore Mycobacterium
Escherichia
Activate
complement
Interfere with
alternative pathway
Fully sialylated
surface
Neisseria
Inactivate Elastase Pseudomonas
Antigen projects
beyond surface
Activation occurs
at the wrong site
Gram-negatives
Interfere with
complement-
mediated
phagocytosis
C3b receptor
competition,
microbe and
phagocyte
Streptococcus