I. BACTERIAL PATHOGENESIS
B. VIRULENCE FACTORS THAT PROMOTE BACTERIAL COLONIZATION OF THE HOST
5. The ability to resist innate immune defenses such as phagocytosis and complement
c. The ability to resist phagocytic destruction
The overall purpose of this Learning Object is:
1) to learn how the ability to resist destruction by phagocytic cells and proteins of the complement pathways plays a role in bacterial pathogenicity by promoting colonization; and
2) to introduce several examples of medically important bacteria that are able to resist phagocytic destruction in order to promote colonization.
LEARNING OBJECTIVES FOR THIS SECTION
In this section on Bacterial Pathogenesis we are looking at virulence factors that promote bacterial colonization of the host. The following are virulence factors that promote bacterial colonization of the host .
1. The ability to use motility and other means to contact host cells and disseminate within a host.
2. The ability to adhere to host cells and resist physical removal.
3. The ability to invade host cells.
4. The ability to compete for iron and other nutrients.
5. The ability to resist innate immune defenses such as phagocytosis and complement.
6. The ability to evade adaptive immune defenses.
Some bacteria are able to resist phagocytosis and interfere with the body's complement pathways. We will break this down into two categories:
1. The ability to resist phagocytic engulfment (attachment and ingestion)
2. The ability to resist phagocytic destruction
We will now look at the ability of bacteria to resist phagocytic destruction and complement serum lysis.
5. The Ability to Resist Innate Immune Defenses such as Phagocytosis and Complement
c. The Ability to Resist Phagocytic Destruction
Bacteria resist phagocytic destruction and complement serum lysis by a variety of means.
a. Resisting phagocytic destruction: preventing fusion of the lysosome with the phagosome
- Once Salmonella is engulfed by macrophages and placed in a phagosome, the bacterium uses its type 3 secretion system to inject proteins that prevent the lysosomes from fusing with the phagosomes, thus providing a safe haven for Salmonella replication within the phagosome and protecting the bacteria from antibodies and other defense elements (see Fig. 2D).
- Legionella pneumophila (inf), after being ingested by macrophages and placed in a phagosome, uses a type 4 secretion system to inject effector proteins that prevent the lysosomes from fusing with the phagosomes and turning the macrophage into a safe haven for bacterial replication.
- Neisseria gonorrhoeae produces Por protein (protein I) that prevents phagosomes from fusing with lysosomes enabling the bacteria to survive inside phagocytes.
- Cell wall lipids of Mycobacterium tuberculosis, such as lipoarabinomannan, arrest the maturation of phagosomes preventing delivery of the bacteria to lysosomes.
- Some bacteria, such as species of Salmonella (inf), Mycobacterium (inf), Legionella (inf), and Chlamydia (inf), block the vesicular transport machinery that enables the lysosome to move to the phagosome for fusion.
b. Resisting phagocytic destruction: escaping from the phagosome
- Some bacteria, such as Shigella flexneri (inf), Listeria monocytogenes (inf), and the spotted fever Rickettsia (inf), escape from the phagosome into the cytoplasm prior to the phagosome fusing with a lysosome (see Fig. 1).
c. Resisting phagocytic destruction: preventing acidification of the phagosome
- Some bacteria, such as pathogenic Mycobacterium (inf) and Legionella pneumophilia (inf), prevent the acidification of the phagosome that is needed for effective killing of microbes by lysosomal enzymes. (Normally after the phagosome forms, the contents become acidified because the lysosomal enzymes used for killing (acid hydrolases) function much more effectively at an acidic pH.)
d. Resisting phagocytic destruction: resisting killing by lysosomal chemicals
e. Resisting phagocytic destruction: killing the phagocyte
- Some bacteria, such as Salmonella (inf), are more resitant to toxic forms of oxygen and to defensins (def) , the toxic peptides that kill bacteria by damaging their cytoplasmic membranes.
- The carotenoid pigments that give Staphylococcus aureus species its golden color and group B streptococci (GBS) its orange tint shield the bacteria from the toxic oxidants that neutrophils use to kill bacteria.
- Some bacteria are able to kill phagocytes. Bacteria such as Staphylococcus aureus (inf) and Streptococcus pyogenes (inf) produce the exotoxin leukocidin that damages either the cytoplasmic membrane of the phagocyte or the membranes of the lysosomes, resulting in the phagocyte being killed by its own enzymes.
- Shigella (inf) and Salmonella (inf), induce macrophage apoptosis, a programmed cell death.
E-Medicine article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
- Legionella pneumophilia
- Salmonella species
- Shigella species
- Rickettsia rickettsii
- Mycobacterium tuberculosis
- Legionella pneumophilia
- Chlamydia trachomatis
- Streptococcus pyogenes
- Staphylococcus aureus
- Neisseria gonorrhoeae
- Haemophilus influenzae
- Bordetella pertussis
- Neisseria meningitidis
- Group B Streptococcus
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Updated: Aug., 2012
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