Dear student,
This document contains my elaborate notes from all the 12 lectures of the
course ‘Infectious Diseases (AB_471024)’ at VU Amsterdam. The study
corresponding to this course is 2nd or 3rd year Gezondheid en Leven or 3rd
year Biomedical Sciences (bachelor).
The lectures in this document:
1. Introduction (page 1)
2. Bacterial anatomy (page 6) & Requirements for infections (page 11)
3. Bacterial Invasion (page 16)
4. Toxins and other mechanisms of cell and tissue damage (page 22)
5. Viruses; structure, infection-cycle and pathogenesis (page 29)
6. Immunology & Microbial Diagnostics (page 36)
7. Microbial genetics in infections (page 45)
8. Knowledge clips antibiotics (page 52) & FTC antibiotics and
resistance (page 58)
I. Discovery of antibiotics (page 52)
II. Mechanism of action of antibiotics (page 54)
III. Mechanisms of antibiotic resistance (page 56)
9. Emerging and re-emerging diseases (page 63) & strategies for
antigenic variation (page 65)
10. Parasites & pathology (page 69)
11. Fungal Biology (page 74) & Research interest 2022 (of Bart
Krom) (page 78)
12. Vaccine lecture (page 80)
This document is also available in a bundle together with a summary of the
textbook ‘Microbiology; a clinical approach’ from A. Strelkauskas. Important
to know is that the summary I made is of the 1st edition. The coordinator of
the course has said that the 1st edition is as sufficient enough as the 2nd
edition.
Good luck with the exam !
, Study: Biomedical Sciences / Gezondheid en Leven (AB_471024)
Lecture 1: Introduction
With infectious diseases, there is always a battle going on between the pathogen and
the immune system. It is important to know that an infection doesn’t always lead to
disease. To calculate the possibility of disease, the following equation is being used:
Different classes of pathogens
Pathogens can be divided in different classes.
- Bacteria (prokaryote)
- Viruses
- Fungi (eukaryote)
- Parasites (eukaryotes)
o Protozoa (unicellular organisms)
o Worms
- Prions (not discussed in this course)
The picture depicted right, shows the classes ordered by size.
❖ Viruses are per definition not a microorganism, because they need a
host for replication/reproduction!
❖ With a light microscope only protozoa and fungi and bacteria can be
spotted. Viruses are smaller than these organisms and can therefore
only been seen with an electron microscope.
Definitions
Infection: Colonization and growth of a microorganism within a host.
- Does not always cause disease!!
Disease: Damage to the host, that interferes with normal functions of the host (-cell)
Pathogenicity: The ability of a microorganism to inflict damage on its host
- Often referring to genetic components of the pathogen
- Host-independent
Virulence: The extent of damage that a pathogen is able to inflict on its host
- Host-pathogen interactions
- Host-dependent
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,Differences between prokaryotes/eukaryotes
Prokaryotic cell
- No nucleus
- DNA is one circular chromosome
- Additional DNA as plasmids
- Transcription & translation simultaneously in cytoplasm
- Rigid cell wall
Eukaryotic cell
- DNA in nucleus as multiple chromosomes
- Nuclear membrane, organelles
- Transcription in nucleus
- Translation in cytoplasm
- Cell wall only in fungi and plants
Viruses and bacteria have different shapes
Viruses:
Bacteriophages: viruses that infect
bacteria
Bacteria:
Characterization of bacteria by staining
The most used technique to stain and therefore distinguish bacteria is gram-staining. This is
used because bacteria can be divided in gram negative and gram positive bacteria. But, what is
the difference between gram positive and negative?
2
,Difference gram positive and gram negative bacteria
Gram-positive bacteria contain a thick wall named the peptidoglycan. They do not have an outer
membrane.
Gram-negative bacteria do contain an outer membrane, but in turn have a thin peptidoglycan
layer.
The process of gram-staining
1. To a mixture of gram negative(gram-) and gram positive(gram+) bacteria, crystal violet is
applied. This makes all the bacteria purple.
2. Next, iodine is applied that forms complexes with the crystal violet stain. In this stage, the
bacteria still remain purple.
3. Next alcohol is administered, resulting in the crystal violet stain to be washed away from
the gram- bacteria.
a. The reason why the stain is washed away with gram- bacteria, is because the
stain works on the peptidoglycan layer. Because gram+ bacteria have a much
thicker peptidoglycan layer, the stain will remain on.
4. Lastly, a counterstain (safranin) is applied, that stains the gram- bacteria and makes
them pink/red.
Under the microscope, the final result kind of looks like this:
3
,General properties of pathogens
Robert Koch (1843-1910), a scientist that won the nobel prize in Physiology or Medicine in 1905
‘for his investigations and discoveries in relation to tuberculosis’ has done the following things
• He was the first to show the link between microbes and disease
• Identified the causative agents of anthrax and tuberculosis
• Developed techniques for obtaining pure cultures
• Established the Koch’s postulates
Koch’s postulates
These postulates are four criteria designed to establish a causative relationship between
a microbe and a disease.
1. The same pathogen must be present in every case of the disease, but not in healthy
individuals
2. The pathogen must be isolated from the sick host and grown in a pure culture
3. The pure pathogen must cause the same disease when given to uninfected hosts
4. The pathogen must be re-isolated from the newly infected hosts, and shown to be the
same organisms as isolated initially.
An example of working according to Koch’s postulates is shown under here:
For some infectious diseases, the Koch’s postulates do not hold true.
- For some pathogens, no animal model is available (chlamydia)
- Some bacteria do not grow in the lab (mycobacterium leprae)
- Viruses need host cells to grow them in the lab (against postulate 2)
- Some pathogens are present in healthy individuals, but are dormant (Streptococcus
Pneumoniae)
Pathogens can also be divided in their targets.
Primary pathogens: These cause diseases in everyone (including healthy individuals)
Opportunistic pathogens: these cause diseases in weakened individuals or when in an unusual
location.
4
, Examples of opportunistic pathogens
Virulence factors
As said before, Virulence is the extent of
damage a pathogen can inflict with its
host. Virulence factors are molecules of
pathogenic microorganisms that increase
the success of infection
- They are often specific to
pathogenic microorganisms
- They frequently interact with host
cells
- They are often on the surface or
excreted
Extracellular vs. intracellular pathogens
Intracellular survival
- Hiding from the immune system
- Invasion: penetrating deeper
tissue
Extracellular survival
- Confrontation with the immune system
- Self-protection: e.g. capsule, cell wall components
- Weapons: e.g. enzymes and toxins
- Antigenic variation
Two extreme strategies for infection
1. Causing acute infection: multiply as fast as possible and spread rapidly
> a lot of damage
2. Causing chronic or persistent infection: staying in the host for a long time:
> causing as little damage as possible
Frontal: confront immune system, often resulting in acute infection
Stealth: hide from immune system, often resulting in chronic infection
The less virulent a pathogen is, the more chance there is for it to transmit to other hosts!
5
,Lecture 2.1: Bacterial anatomy
Why is the bacterial anatomy important?
A variety of bacterial structures play an important role in infection. Also, many bacterial
structures are recognized by the immune system.
The bacterial cell envelope
(more info about the differences on page 3).
Peptidoglycan
Peptidoglycan is often referred to as the bacterial cell wall. It
consists of two sugar molecules:
- N-acetyl glucosamine (NAG)
- N-acetyl muramic acid (NAM)
Peptides connected to these sugars establish crosslinking in the
peptidoglycan layer.
Only the NAM saccharides do peptides bind. These peptides
differ between gram+ and gram- bacteria.
The peptidoglycan:
- Gives firmness to the cell
- Protects against osmotic changes and other environmental stresses
6
, Gram- outer membrane
The outer membrane of gram- bacteria consists of lipids and proteins. The proteins can be
integral or lipoproteins.
- Lipoproteins have a lipid tail and are
attached to both the peptidoglycan and
outer membrane.
The outer membrane is a lipid bilayer whose
inner layer consists of phospholipids and the
outer layer consists of lipopolysaccharides
(LPS). The membrane serves as a barrier against
external factors (host factors, antibiotics)
- Porins form channels in the outer
membrane where they mediate the import
and export of molecules.
The inner leaflet consists of lipid molecules
The outer leaflet consists of polar headgroups
- This one is mainly composed of LPS
LPS
LPS consists of three domains.
1. Lipid A: this is the anchor. It is responsible for making the outer membrane
a. Lipid A is also called endotoxin → it doesn’t have a really toxic function, but the
immune system is able to recognize the LPS really good. This overreaction can
then become toxic.
Furthermore, two types of sugar domains stick out the outer membrane
2. Core polysaccharide: this domain is very constant between bacteria
3. O-specific polysaccharide: this domain is variable. It also serves as an anti-antibiotic
mechanism, because this polysaccharide makes it unrecognizable for certain antibiotics.
a. It has a role in attachment to host cells
b. It can be recognized by adaptive immune system.
The outer structures of the bacterial cell envelope
There are two structures particularly involved in adhesion
- Glycocalyx/Capsule
- Fimbriae/Pili
Two structures particularly involved in mobility
- Flagellas
- Axial filaments
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