General Bacteriology:

Pathogenesis of Bacterial
Diseases
 Learning objectives

At the end of the session, the students will be able to understand:

▰ Mechanism of microbial pathogenicity

▰ Differences between endotoxins and exotoxins

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Essentials of Medical Microbiology
MECHANISM OF
MICROBIAL
PATHOGENICITY
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Essentials of Medical Microbiology
MECHANISM OF MICROBIAL
PATHOGENICITY

▰ Pathogenicity - refer to the ability of a microbial species to produce

disease.

▰ Virulence - relative degree of pathogenesis (tissue damage), which may

vary between different strains of the same organism depending upon the
expression of the virulence factors.

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Essentials of Medical Microbiology
MECHANISM OF MICROBIAL
PATHOGENICITY (Cont..)

▰ Exaltation- Enhancement of virulence is known as exaltation, which can

be induced experimentally by serial passage into susceptible hosts.

▰ Attenuation - Reduction of virulence which can be achieved by passage

through unfavourable hosts, repeated cultures in artificial media, growth in
high temperature or in the presence of weak antiseptics, desiccation or
prolonged storage in culture.
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Essentials of Medical Microbiology
Mode of transmission of bacterial infections
Transmission Bacterial agents/diseases

Contact Multi-drug resistant organisms in hospitals such as S. aureus, E. coli,

Klebsiella, etc. , Bacillus anthracis
Droplet C. diphtheriae ,Pneumococcus ,Meningococcus

Aerosol M. tuberculosis

Ingestion Salmonella and Shigella ,Vibrio ,Campylobacter ,Agents of food poisoning

Vector-borne Rickettsiae ,Borrelia

Sexual Gonococcus ,Chlamydia trachomatis,Treponema pallidum ,Haemophilus

ducryei
Vertical Treponema pallidum

Birth canal Listeria , Streptococcus agalactiae

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Essentials of Medical Microbiology
Infective Dose

▰ Minimum inoculum size that is capable of initiating an infection.

Low infective dose:

▰ Shigella: Very low (as low as 10 bacilli)

▰ Escherichia coli O157: H7 (<10 bacilli)

▰ Campylobacter jejuni (500 bacilli).

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Essentials of Medical Microbiology
Infective Dose (Cont..)

Large Infective dose

▰ Escherichia coli (106 - 108 bacilli)

▰ Salmonella (102 – 105 bacilli)

▰ Vibrio cholerae (106 - 108 bacilli).

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Essentials of Medical Microbiology
Infective Dose (Cont..)

Infective dose varies depending upon the factors, such as:

▰ Virulence of the organism

▰ Host’s age and overall immune status

▰ Ability of the organism resisting the gastric acidity

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Essentials of Medical Microbiology
Adhesion
▰ Adhesion of the bacteria to body surfaces - initial event in the pathogenesis
of the disease.
o Mediated by specialized molecules - adhesins - bind to specific host
cell receptors.
o Adherence prevents the bacteria from being flushed away in secretions
and also facilitates bacterial invasion into the host cells.

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Essentials of Medical Microbiology
Adhesion (Cont..)

Structures which help in adhesion:

▰ Fimbriae or pili

▰ Non-pilus adhesins

▰ Biofilm formation

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Essentials of Medical Microbiology
Invasion

▰ Refers to entry of bacteria into host cells, leading to spread within the host
tissues.

▰ Highly invasive pathogens produce spreading or generalized lesions, while

less invasive pathogens cause localized lesions.

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Essentials of Medical Microbiology
Invasion (Cont..)

Important virulence factors that help in invasion include:

▰ Virulence marker antigen or invasion plasmid antigens in Shigella

▰ Enzymes: Invasion of bacteria is enhanced by many enzymes such as:

hyaluronidase, collagenase, streptokinase, IgA proteases.

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Essentials of Medical Microbiology
Invasion (Cont..)
Antiphagocytic Factors: Bacteria are rapidly killed once they are ingested by
phagocytes. Some pathogens develop strategies to evade phagocytosis by
several antiphagocytic factors, the most important ones being –

▰ Capsule

▰ Cell wall proteins

▰ Cytotoxins
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Essentials of Medical Microbiology
Intracellular Survival
Mechanism of intracellular survival Organism
Inhibition of phagolysosome fusion Legionella species
Mycobacterium tuberculosis
Chlamydia species
Resistance to lysosomal enzymes Salmonella Typhimurium
Coxiella species
Mycobacterium leprae
Adaptation to cytoplasmic replication Listeria, Rickettsia
Francisella tularensis

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Essentials of Medical Microbiology
Intracellular Survival (Cont..)

Facultative intracellular bacteria Obligate intracellular

Salmonella Typhi, Brucella Mycobacterium leprae
Legionella, Listeria, Nocardia Rickettsia
Neisseria meningitidis, Yersinia Chlamydia
Mycobacterium tuberculosis Coxiella burnetii

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Essentials of Medical Microbiology
Toxins
Endotoxins

▰ They are the lipid A portion of lipopolysaccharide. They are present as an

integral part of the cell wall of Gram negative bacteria.

▰ They are released from the bacterial surface by natural lysis of the bacteria
and are responsible for various biological effects in the host.

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Essentials of Medical Microbiology
Toxins (Cont..)

Effects of bacterial endotoxins

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Essentials of Medical Microbiology
Toxins (Cont..)
Biological effects of endotoxins:
▰ Macrophage activation
▰ Complement activation
▰ Endothelial activation
▰ Coagulation pathways activation
▰ Platelet activation
▰ Mast cell activation
▰ In Gram negative septicemia
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Essentials of Medical Microbiology
Toxins (Cont..)
Exotoxins

▰ Heat labile proteins; secreted by certain species of both gram-positive and

gram-negative bacteria and diffuse readily into the surrounding medium.

▰ High potency

▰ Used for vaccine

▰ Specific action
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Essentials of Medical Microbiology
Bacterial exotoxins and their mechanism of
action
Organisms Toxins (Exotoxins) Mechanism

Staphylococcus aureus Enterotoxin, Toxic shock syndrome toxin Act as super antigen; stimulate T cell non-
specifically, to release of large amounts of
Streptococcus pyogenes Streptococcal pyrogenic exotoxin cytokines.
Corynebacterium diphtheriae Diphtheria toxin (DT) Inhibits protein synthesis (by inhibiting
elongation factor-2)
Bacillus anthracis Anthrax toxin ↑cAMP in target cell, edema

Clostridium perfringens α toxin and other major and minor toxins Lecithinase and phospholipase activity →
causes myonecrosis
Clostridium tetani Tetanus toxin (tetanospasmin) Decrease in neurotransmitter (GABA and
glycine) release from
the inhibitory neurons → spastic paralysis

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Essentials of Medical Microbiology
Bacterial exotoxins and their mechanism of
action (Cont..)
Organisms Toxins (Exotoxins) Mechanism
Clostridium botulinum Botulinum toxin Decrease in neurotransmitter (acetyl choline) release from
neurons → flaccid paralysis
Escherichia coli Heat labile toxin (LT) Activation of adenylate cyclase → ↑cAMP in target cell →
(diarrheagenic) secretory diarrhea
Heat stable toxin (ST) ↑cGMP in target cell → secretory diarrhea

Verocytotoxin Inhibit protein synthesis (by inhibiting ribosome)

Shigella dysenteriae type- Shiga toxin

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Vibrio cholerae Cholera toxin (CT) Activation of adenylate cyclase → ↑cAMP in target cell →
secretory diarrhea
Pseudomonas Exotoxin-A Inhibit protein synthesis (by inhibiting elongation factor-2)

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Essentials of Medical Microbiology
Differences between bacterial endotoxins and
exotoxins
Feature Endotoxins Exotoxins
Nature Lipopolysaccharides Proteins

Source Part of cell wall of Gram negative bacteria Secreted both by Gram positive & negative
bacteria; diffuse into surrounding medium
Released by Cell lysis , Not by secretion Actively secreted by the bacteria

Heat stability Highly stable Heat labile destroyed at 60 oC

Mode of action ↑IL-1 and TNF Mostly enzyme like action

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Essentials of Medical Microbiology
Differences between bacterial endotoxins and
exotoxins (Cont..)
Feature Endotoxins Exotoxins
Effect Non-specific (fever, shock, etc) Specific action on particular tissues

Tissue affinity No Specific affinity for tissues

Fatal dose Only large doses are fatal More potent, even smaller doses- fatal

Antigenicity Poorly antigenic Highly antigenic

Neutralisation by Ineffective Neutralized by specific antibodies

antibodies
Used for vaccine No effective vaccine is available using Toxoid forms are used as vaccine; e.g. tetanus
endotoxin toxoid

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Essentials of Medical Microbiology
Questions:
▰ Q1. Chemical nature of endotoxin is:

a. Lipopolysaccharide

b. Protein

c. Carbohydrate

d. None

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Questions:
▰ Q2. Obligate intracellular bacteria are all, except::

a. M. leprae

b. Rickettsia

c. Chlamydia

d. M. tuberculosis

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Questions:
▰ Q3. Correct about exotoxins:

a. Made of lipopolysaccharides

b. Have enzyme like action

c. Poorly antigenic

d. Highly stable

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