Transcript Microbial Mechanisms of Pathogenicity

Medical biology, microbiology, virology,
immunology department
Microbial Mechanisms
of Pathogenicity
by As.Prof. O.V. Pokryshko
Main Features
of Pathogenic Microorganisms.
Pathogenicity. This is the potential
capacity of certain species of microbes to
cause an infectious process.
Virulence signifies the degree of
pathogenicity of the given culture (strain).
Virulence, therefore, is an index of the
qualitative individual nature of the pathogenic
microorganism. Virulence in pathogenic
microbes changes under the influence of
natural conditions.
The virulence of pathogenic
microorganisms is associated with
 adherence,
 invasiveness,
 capsule production,
 toxin production,
 aggressiveness
 and other factors.
The adherence
Adherence factor
Filamentous
hemagglutinin
Fimbriae
Glycocalyx or capsule
Pili
Slime
Description
Causes adherence to
erythrocytes
Help attach to solid bacteria to
solid surfaces
Inhibits phagocytosis and aids in
adherence
Bind bacteria together for
transfer of genetic material
Tenacious bacterial film that is
less compact than a capsule
Teichoic and lipoteichoic Cell wall components in gram
acid
positive bacteria that aid in
adhesion
Adherence bacteria to cell surfaces
Adherence of vibrio cholera on the mucose
Capsule production
Capsule
production
makes the microbes
resistant to phagocytosis
and
antibodies,
and
increases their invasive
properties.
Thus, for example,
capsular anthrax bacilli
are not subject to
phagocytosis,
while
noncapsular variants are
easily phagocytized.
The role of capsular material
in bacterial virulence.
Some
pathogenic
microorganisms
(B. anthracis, C. perfringens, S. pneumoniae, causative agents of plague and
tularaemia) are capable of producing a
capsule in animal and human bodies.
Certain microorganisms produce capsules
in the organism as well as in nutrient media
(causative agents of rhinoscleroma,
ozaena, pneumonia).
Invasive properties of pathogenic bacteria
Virulent microbes are characterized by
the ability to penetrate tissues of the
infected organism (invasive properties).
collagenase and hyaluronidase
immunoglobulin A protease
leukocidins
M-protein
protein A
Collagenase
and
hyaluronidase
degrade collagen and hyaluronic acid,
respectively,
thereby
allowing
the
bacteria to spread through subcutaneus
tissue
(Streptococci,
Staphylococci,
Clostridium ).
Immunoglobulin A protease degrades
IgA, allowing the organism to adhere to
mucous membranes, and is produseed
chiefly by N. gonorrhoeae, Haemophilus
influenzae, and S. pneumoniae.
Leukocidins
neutrophilic
macrophages.
can
destroy
leukocytes
M-protein
of
antiphagocytic.
S.
pyogenes
both
and
is
Protein A of S. aureus binds to IgG
and
prevents
the
activation
of
complement.
Coagulase, which is produced by S. aureus and accelerate
the formation of a fibrin clot from its precursor, fibrinogen (this clot
may protect the bacteria from phagocytosis by walling off the
infected area and by coating the organisms with a layer of fibrin)
The invasion of cells by bacteria
Toxin production
According to the nature of production,
microbial toxins are subdivided into
exotoxins and endotoxins.
More than 50 protein exotoxins of
bacteria are known to date.
Exotoxins easily diffuse from the cell
into the surrounding nutrient medium.
They are characterized by a markedly
distinct toxicity, and act on the
susceptible organism in very small doses.
Exotoxins have the properties of
enzymes hydrolysing vitally important
components of the cells of tissues and
organs.
Exotoxins exert their effects in a
variety of ways – by inhibition of protein
synthesis, inhibition of nerve synapse
function, disruption of membrane transport, damage to plasma membranes.
Exotoxins may be devided into fifth
categories on the basis of the site affected:
 neurotoxins (tetanotoxin, botulotoxin)
C. tetani, C. botulinum, B. cereus, S. aureus;
 cytotoxins (enterotoxins, dermatonecrotoxin)
E. coli, Salmonella spp., Klebsiella spp., V.
cholerae, C. perfringens;
 functional blocators (cholerogen),
V. cholerae;
 membranotoxins (hemolysins, leucocidin),
S. aureus;
 exfoliatin
S. aureus.
Action of the hemolysin on red blood cells
MICROORGANISM
TOXIN
DISEASE
ACTION
Clostridium
botulinum
Several
neurotoxins
Botulism
Paralysis; blocks neural
transmission
Clostridium tetani
Neurotoxin
Tetanus
Spastic paralysis; interferes
with motor neurons
Corynebacterium
diphtheriae
Cytotoxin
Diphtheria
Bordetella
pertussis
Pertussis
toxin
Whooping cough
Blocks G proteins that are
involved in regulation of cell
pathways
Streptococcus
pyogenes
Hemolysin
Scarlet fever Food
Lysis of blood cells
Staphylococcus
aureus
Enterotoxin
Poisoning
Aspergillus flavus
Cytotoxin
Aflatoxicosis
Amanita
phalloides
Cytotoxin
Mushroom food
poisoning
Blocks protein synthesis
Intestinal inflammation
Blocks transcription of DNA,
thereby stopping protein
synthesis
Blocks transcription of
DNA,thereby stopping
protein synthesis
Endotoxins
 are more firmly
 bound with the body of the
bacterial cell,
 are less toxic and act on the
organism in large doses;
 their latent period is usually
estimated in hours,
 the selective action is poorly
expressed.
According to chemical structure,
endotoxins are related to glucoside-lipid
and polysaccharide compounds or
phospholipid-protein complexes.
They
are
thermostable.
Some
endotoxins withstand boiling and
autoclaving at 120°C for 30 minutes.
Action of the endotoxin
Endotoxin in the bloodstream
Differences between exotoxins and endotoxins
exotoxins
endotoxins
Proteins
Heat labile
Lipopolysaccharides
Heat stable
Actively secreted by cells,
diffuse into surrounding
medium
form part of cell wall,do
not diffuse into
surrounding medium
Readily separable from
cultures by physical
means such as filtration
Action often enzymic
Obtained only by cell
lysing
Specific pharmacological
effect for each exotoxin
Non-specific action of all
endotoxins
No enzymic action
Specific tissue affinities
Active in very minute
doses
Highly antigenic
No specific tissue affinity
Active only in very large
doses
Weakly antigenic
Stimulate formation of
Do not stimulate formation
antitoxin which neutralizes of antitoxin
toxin
Converted into toxoid by
Can not be toxoided
formaldehyde
Produced by both grampositive bacteria and
gram-negative bacteria
Frequently controlled by
extrachromosomal genes
(e.g. plasmids)
Produced by gramnegative bacteria only
Synthesis directed by
chromosomal genes
genes
In characterizing pathogenic microbes a unit of
virulence has been established.
 Dlm (Dosis letalis minima), representing the
minimum amount of live microbes which in a certain
period of time bring about 95-97 % death of the
corresponding laboratory animals.
 the absolute lethal dose of pathogenic microbe
Dcl (Dosis certa letalis) which will kill 100 % of the
experimental animals has been established.
 At present LD50 (the dose which is lethal to one
half of the infected animals) is considered to be the
most suitable, and may serve as an objective criterion
for comparison with other units of virulence.