The document discusses bacterial pathogenesis and virulence. It describes three main ways bacteria cause disease: 1) invasiveness through mechanisms like adhesion and toxin production, 2) toxigenesis through exotoxins and endotoxins, and 3) evading host immune responses. Specific virulence factors and pathogenesis mechanisms are discussed for different bacteria like Pseudomonas aeruginosa and Mycobacterium tuberculosis. The host barriers bacteria must overcome include phagocytosis, complement activation, and adaptive immune responses; bacteria have evolved strategies to inhibit or subvert these defenses.

1. BACTERIAL PATHOGENESIS
LECTURE 2
BLS 1st & 2ND YR 2008/09
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2. Why we do not get ill?
(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
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3. Introduction
A pathogen 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. Introduction
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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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
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.
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7. Mechanisms of Bacterial Pathogenicity
2. Toxigenesis: ability to produce toxins.
Bacteria may produce two types of toxins:
i. exotoxins and
ii. endotoxins.
 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. Mechanisms of Bacterial Pathogenicity
 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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9. 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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10. Big person in microbiology
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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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
 Ingestion: Salmonella, Shigella, Vibrio, Clostridium etc..
 Inhalation: Mycobacterium, Mycoplasma, Chlamydia etc..
 Trauma: Clostridium tetani
 Arthropod bite: Rickettsia, Yersinia pestis, etc.
 Sexual transmission: Neisseria gonorrboeae, HIV,
chlamydia, etc
 Needle stick: Staphylococcus, HIV, HBV
 Maternal-neonatal: HIV, HBV, Neisseria, etc.
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14. Modes of infectious disease transmission
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
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15. Extracellular versus Intracellular Parasitism
 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.
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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
Host cell Taken up by Inhibitory Mycobacterium
membrane phagocyte molecule
and resist killing
Production Degrade IgA protease Streptococcus
Of antibody antibody
Antimicrobial Activate T cells Superantigen Staphylococcus
cell-mediated non-specifically
response and
Productively
Antimicrobial Vary presenting Switch on Borrelia
immune microbial production of
response antigen different
antigens
Genetic Streptococcus
recombination
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18. Virulence factors
Factors enhancing the ability of bacteria to cause disease
Example: Pseudomonas aeruginosa
 Adhesins: attachment
 Alginate production: mucoid layer
 Exotoxin A: 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
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19. Pathogenic action of bacteria
 Tissue destruction: flesh-eating bacteria:
Clostridium perfrigens
 Obstruction: Cytic fibrosis
 Toxins: bacterial components that 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. Endotoxin: lipopolysaccharide
IL-1 Pseudomonas aeruginosa
TNF
Fever
Disseminated intravascular coagulation
Septic shock
death
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22. Superantigens
Secreted proteins
(exotoxins) that exhibit
highly potent lymphocyte-
transforming (mitogenic)
activity directed towards T
lymphocytes.
Polyclonal T cell activation
Aberrant cytokines, Antigen
/MHC-1
cell death
Specific T cell activation
Anti-microbes immunity
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23. Known and suspected association of superantigens with
animal diseases
Autoimmune diseases
Lyme disease
Multiple sclerosis
Acute diseases
Food poisoning:
Staph infections
Streptococal
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24. EVASION STRATEGIES (1)
Defence Microbial strategy Mechanism Example
Wash-out Bind to cell Adhesins Neisseria
Inhibit ciliary Ciliotoxic/ Bordetella
activity Ciliostatic Streptococcus
molecule
Disrupt Leucocidins Staphylococcus
Chemotaxis
Ingestion cytotoxic
and
killing by
phagocyte
Inhibit Capsule Streptococcus
phagocytosis
Inhibit lysosomal Inhibitory Mycobacterium
fusion molecule
Multiply Unknown Listeria
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25. EVASION STRATEGIES (2)
Defence Microbial strategy Mechanism Example
Restrict Fe- Compete Siderophore Mycobacterium
Lactoferrin Escherichia
Transferrin
Interfere with Fully sialylated Neisseria
Activate alternative pathway surface
complement
Inactivate Elastase Pseudomonas
Antigen projects Activation occurs Gram-negatives
beyond surface at the wrong site
Interfere with C3b receptor Streptococcus
complement- competition,
mediated microbe and
phagocytosis phagocyte
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