Molecular Basis of Bacterial Infections Evelien Floor
Bacterial immune evasion
Bacterial immune evasion is the process by which bacteria avoid and/or antagonize the host’s
immune response. The evolutionary advantage of bacteria compared to humans is that they divide
approximately every 20 minutes which allows them to adapt to the host. There are four mechanisms
to evade the immune system:
1. Capsule
2. Intracellular
3. Change surface
4. Secrete modulators
There are some bacteria that combine all mechanisms
Capsule
The capsule provides bacteria with protection form the host immune response as well as antibiotics.
Capsules are inert high molecular weight glycopolymers that surround the whole bacterium. Some
exceptions have capsules with immunomodulatory properties. The capsule protects from:
Desiccation
Phage attack
Complement lysis
Phagocytosis
There are three types of bacteria that consist of a capsule:
Streptococcus pneumoniae (pneumococcus)
Neisseria meningitidis (meningococcus)
Pseudomonas aeruginosa
Streptococcus pneumoniae consists of the thickest capsule of all three.
Some capsule-glycopolymers have been used with great success as vaccine components. Once
induced, anti-capsular antibodies, in concert with complement, attack the outside of the bacterium
and subsequent phagocytosis can occur. However, there are more types of capsules in some
bacterial species so that is hard to cover in one vaccine.
The capsule is not that tight that nothing can go through, antibodies and complement can still bind to
the bacteria. Because of the capsule, the receptors on the phagocyte are too far away from the
antibodies bound to the bacterium. Therefore, phagocytosis will not occur.
Not all bacteria consist of a capsule because capsules are energy-wise very expensive. As a
bacterium, you have to let go of your capsule when you want to adhere to surfaces or cells so there
is constant renewing of the capsule sugars.
Intracellular
Some bacteria are able to live inside the cell and hide from the immune system. They invade host
cells actively with their flagella and attach to the cell. Afterwards, the host cell will ingest the
bacterium. Internalisation takes place via complement receptors, not via Fc receptors because then
degradation would take place. Once in the cell they are present in the cytoplasm or in a vacuole; the
phagosome or phagolysosome.
Special tricks are needed to survive inside the host cell:
Resist ROS attack (Staphylococci)
Resist anti-microbial peptides (AMP) (Salmonella)
Resist/reverse lysosome acidification (Mycobacterium)
Inhibit lysosome fusion (Legionella)
Have alternative metabolic pathways (Listeria)
1
, Molecular Basis of Bacterial Infections Evelien Floor
Escape to cytosol (Listeria and Legionella)
Despite all those mechanisms there is also an intracellular innate immune system that can detect and
kill the bacterium. Intracellular systems are: NOD-like receptors, TLR9, inflammasome and anti-
microbial peptides).
Change surface
Another mechanism is to change surface structures in order to evade immune recognition. These
surface structures are structures that are normally recognized by components of the innate immune
system. This makes the bacterium invisible.
An example of this mechanism is the change of LPS. LPS is present on all Gram-negative bacteria.
Some bacteria modify LPS so that it is no longer recognized by TLR4-MD2, but still retains its
important structural role in the integrity and impermeability of the outer membrane. This change is
adding more phosphate groups or making longer fatty acid chains.
In S. aureus, MprF adds an L-Lysine to the phosphatidylglycerol lipid in the bacterial membrane.
Afterwards, the positively charged lysine residue acts as an electrostatic buffer that provides
resistance to the cationic human defensin molecules.
A disadvantage is that there is a delicate balance between a functional antigen and a structure that
has lost its important function or properties because of escape mutations.
Secrete modulators
Secreted modulators are usually proteins with one of the following effects:
Anti-phagocytosis
Anti-chemotactic proteins
Anti-opsonic actions
o Inhibit action of antibodies
o Inhibit complement activation
o Cleave antibodies/complement
Kill phagocytes
A disadvantage of secreting modulators is that sometimes it is difficult to reach sufficiently high
concentrations. In addition, other bacteria might profit from these secreted factors.
Innate immunity
Innate immunity is important to eliminate bacteria right away. Phagocytes kill bacteria within 10-20
seconds. There are 10 million phagocytes present per mL blood, 60% of them is neutrophil.
Complement proteins can kill bacteria within ten seconds. Antimicrobial peptides can kill within 2
seconds.
The hundreds of different bacterial
receptors can be recognized by the
immune system because it are
evolutionary conserved structures.
LPS
LPS is released in vesicles. Mammals have
evolved a system to recognize LPS. LBP can
take one monomer of LPS and transfer it to
CD14 which is on the membrane of
2
Bacterial immune evasion
Bacterial immune evasion is the process by which bacteria avoid and/or antagonize the host’s
immune response. The evolutionary advantage of bacteria compared to humans is that they divide
approximately every 20 minutes which allows them to adapt to the host. There are four mechanisms
to evade the immune system:
1. Capsule
2. Intracellular
3. Change surface
4. Secrete modulators
There are some bacteria that combine all mechanisms
Capsule
The capsule provides bacteria with protection form the host immune response as well as antibiotics.
Capsules are inert high molecular weight glycopolymers that surround the whole bacterium. Some
exceptions have capsules with immunomodulatory properties. The capsule protects from:
Desiccation
Phage attack
Complement lysis
Phagocytosis
There are three types of bacteria that consist of a capsule:
Streptococcus pneumoniae (pneumococcus)
Neisseria meningitidis (meningococcus)
Pseudomonas aeruginosa
Streptococcus pneumoniae consists of the thickest capsule of all three.
Some capsule-glycopolymers have been used with great success as vaccine components. Once
induced, anti-capsular antibodies, in concert with complement, attack the outside of the bacterium
and subsequent phagocytosis can occur. However, there are more types of capsules in some
bacterial species so that is hard to cover in one vaccine.
The capsule is not that tight that nothing can go through, antibodies and complement can still bind to
the bacteria. Because of the capsule, the receptors on the phagocyte are too far away from the
antibodies bound to the bacterium. Therefore, phagocytosis will not occur.
Not all bacteria consist of a capsule because capsules are energy-wise very expensive. As a
bacterium, you have to let go of your capsule when you want to adhere to surfaces or cells so there
is constant renewing of the capsule sugars.
Intracellular
Some bacteria are able to live inside the cell and hide from the immune system. They invade host
cells actively with their flagella and attach to the cell. Afterwards, the host cell will ingest the
bacterium. Internalisation takes place via complement receptors, not via Fc receptors because then
degradation would take place. Once in the cell they are present in the cytoplasm or in a vacuole; the
phagosome or phagolysosome.
Special tricks are needed to survive inside the host cell:
Resist ROS attack (Staphylococci)
Resist anti-microbial peptides (AMP) (Salmonella)
Resist/reverse lysosome acidification (Mycobacterium)
Inhibit lysosome fusion (Legionella)
Have alternative metabolic pathways (Listeria)
1
, Molecular Basis of Bacterial Infections Evelien Floor
Escape to cytosol (Listeria and Legionella)
Despite all those mechanisms there is also an intracellular innate immune system that can detect and
kill the bacterium. Intracellular systems are: NOD-like receptors, TLR9, inflammasome and anti-
microbial peptides).
Change surface
Another mechanism is to change surface structures in order to evade immune recognition. These
surface structures are structures that are normally recognized by components of the innate immune
system. This makes the bacterium invisible.
An example of this mechanism is the change of LPS. LPS is present on all Gram-negative bacteria.
Some bacteria modify LPS so that it is no longer recognized by TLR4-MD2, but still retains its
important structural role in the integrity and impermeability of the outer membrane. This change is
adding more phosphate groups or making longer fatty acid chains.
In S. aureus, MprF adds an L-Lysine to the phosphatidylglycerol lipid in the bacterial membrane.
Afterwards, the positively charged lysine residue acts as an electrostatic buffer that provides
resistance to the cationic human defensin molecules.
A disadvantage is that there is a delicate balance between a functional antigen and a structure that
has lost its important function or properties because of escape mutations.
Secrete modulators
Secreted modulators are usually proteins with one of the following effects:
Anti-phagocytosis
Anti-chemotactic proteins
Anti-opsonic actions
o Inhibit action of antibodies
o Inhibit complement activation
o Cleave antibodies/complement
Kill phagocytes
A disadvantage of secreting modulators is that sometimes it is difficult to reach sufficiently high
concentrations. In addition, other bacteria might profit from these secreted factors.
Innate immunity
Innate immunity is important to eliminate bacteria right away. Phagocytes kill bacteria within 10-20
seconds. There are 10 million phagocytes present per mL blood, 60% of them is neutrophil.
Complement proteins can kill bacteria within ten seconds. Antimicrobial peptides can kill within 2
seconds.
The hundreds of different bacterial
receptors can be recognized by the
immune system because it are
evolutionary conserved structures.
LPS
LPS is released in vesicles. Mammals have
evolved a system to recognize LPS. LBP can
take one monomer of LPS and transfer it to
CD14 which is on the membrane of
2
