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Summary Microbial infection and pathogenesis, antibiotics

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Summary about the lecture about microbial infection and pathogenesis, antibiotics including summary for the corresponding literature.

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  • 18 januari 2021
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  • 2020/2021
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HC9 Microbial infection and
Pathogenesis, Antibiotics (BOOK)
Chapter 25.1-25.8, 5.17 & 28.10-28.12

CH5 Microbial Infection and Pathogenesis
25.1 Microbial Adherence
Infection is the growth of microorganims on or in the host and disease is actual tissue damage or
injuries that impairs host function.

Adherence is the fist step and required to initiate disease, however it is not sufficient to initiate
disease because the host has many defences.

Adherence is the enhanced ability of a microorganism to attach to a cell or a surface.
Receptors on the pathogen surface are called adhesins and are composed of glycoproteins or
lipoprotein covalently bound to the outer layer of the cell. Host cell receptors are typically
glycoproteins or complex membrane lipids.

Some notable pathogenic bacteria form a capsule which facilitates adherence to host tissues but also
assist in the overall attachment process due to its sticky nature. Besides these functions, they are also
important for protecting the pathogen against the host’s defence system.

Fimbriae and pili are structures that function in attachment. Pili are typically longer and fewer in
number than fimbriae and in addition to attachment, some function in conjugation. Flagella also
seem to play a role, but less sufficient.

25.2 Colonisation and Invasion
Colonisation is the growth of a microbe after it has gained access to host tissues. This process already
begins at birth.
Colonisation typically begins at sites in the mucous membrane, mucous mebranes consist of
epithelial cells which are tightly packed that interface with th external environment.
The epithelial cells in the mucous membrane secrete mucus which contains water-soluble proteins
and glycoproteins.

Dental plaque are thick biofilms formed by oral streptococci which cause the oral microbial disease
dental caries. Dental plaque is a complex mixed-culture biofilm composed of several different genera
of Bacteria and their accumulated products. As dental plaque accumulates, the microbiota produce
locally high concentrations of lactic acid that decalcifies tooth enamel, resulting in dental caries.

Invasion is the ability of a pathogen to enter into host cells or tissues, spread, and cause disease.
The presence of bacteria in the blood is called bacteremia which is self-limiting because the bacteria
do not grow in the bloodstream and therefore the immune system quickly removes them. In
septicemia bacteria multiply in the bloodstream and th organism spreads rapidly.


25.3 Pathogenicity, Virulence, and Attenuation
Pathogenicity is the overall ability to cause disease. The measure of pathogenicity is virulence which
is the relative ability of a pathogen to cause disease.

, Host damage in an infectious disease is mediated by virulence factors which are substances
produced by the pathogen.

The LD50 is defined as the number of cells of a pathogen that kills 50% of the animals in a test group.

The virulence of a pathogen can change, this is called attenuation which is the decrease or loss of
virulence of a pathogen. Attenuation is thought to occur because nonvirulent or weakly virulent
mutants grow faster than virulent strains in laboratory media where virulence has no selective
advantage. However, if an attenuated culture is reinoculated into an animal, it may regain its original
virulence.

25.4 Genetics of Virulence and the Compromised Host
Exotoxins are antiphagocytic proteins that block engulfment of bacterial cells by host phagocytes
which are proteins that promote survival if the bacterium does get phagocytosed. Siderophores are
organic molecules that bind iron tightly and allow the bacteria to outcompete host sequestration
systems for iron.

An injectisome is an organelle in the bacterial envelope that allows for the direct transfer of
virulence proteins into host cells through a needle-like assembly.

A compromised host is an individual in which one or more resistance mechanisms are inactivated
and in whom the probability of infection is therefore increased. Opportunistic pathogens are
microbes that cause disease only in the absence of normal host resistance.




25.5 Enzymes as Virulence Factors
Hyaluronidase is an enzyme that promotes spreading of organisms in tissues by breaking down the
polysaccharide hyaluronic acid.
Collagenase is an enzyme that destroys collagen, which is a major protein of connective tissues in
muscle and other body tissues.
Streptokinase dissolves fimbriae cloths and allow bacterial cells to spread.
Coagulase induces fibrin clotting which allow bacterial cell to remain at the site of infection.
Nuclease break down nucleic acids or lipids.
Proteases break down proteins.

25.6 AB-type Exotoxins
Toxicity is the ability of an organism to cause disease by means of a toxin that inhibits host cell
function or kills host cels. Exotoxins are toxic proteins released from the pathogen as it grows. Some
exotoxins are enterotoxins which are toxic proteins whose site of action is the small intestine,
generally causing secretion of fluid into the intestinal lumen, resulting in vomiting and diarrhea.
Exotoxins fall in three categories:
- AB toxins consist of two subunits; B binds to to host cells, facilitating transfer of the A
subunit which damages the cell.
- Cytolytic toxins
- Superantigen toxins

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