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 and complement serum lysis

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 or complement lysis 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.
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 and serum lysis

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 and Complement Serum Lysis

For More Information: Phagocytosis from Unit 4

For More Information: The Complement Pathways from Unit 4

 

Bacteria resist phagocytic destruction and complement serum lysis by a variety of means.

a. Resisting phagocytic destruction

• Some bacteria, such as Legionella pneumophilia (inf) and Mycobacterium species (inf), cause the phagocytic cell to place them into an endocytic vaculole via a pathway that decreases their exposure to reactive oxygen species (ROS), the oxygen-containig free radicals used by neutrophils to kill bacteria.
• Some bacteria, such as Salmonella (inf), are more resitant to toxic forms of oxygen and to defensins (def) (toxic peptides that kill bacteria).

• Some bacteria, such as Shigella flexneri (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).

GIF animation showing a bacterium resisting phagocytosis by escaping from a phagosome.

• Neisseria gonorrhoeae produces Por protein (protein I) that prevents phagosomes from fusing with lysosomes enabling the bacteria to survive inside phagocytes.

• Some bacteria, such as species of Salmonella (inf), Mycobacterium (inf), Legionella (inf), and Chlamydia (inf), block the vesicular transport machinery that enables the phagosome to fuse with the lysosome.

GIF animation showing a bacterium resisting phagocytosis by blocking the fusion of a lysosome and a 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.)
• The carotenoid pigments that give Staphylococcus aureus its golden color and group B streptococci (GBS) its orange tint shield the bacteria from the toxic oxidants that neutrophils use to kill bacteria.
• Cell wall lipids of Mycobacterium tuberculosis, such as lipoarabinomannan, arrest the maturation of phagosomes preventing delivery of the bacteria to lysosomes.
• 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. On the other hand, bacteria, such as Shigella (inf) and Salmonella (inf), induce macrophage apoptosis, a programmed cell death.

 

b. Resisting complement serum lysis by MAC (def)

• Serum lysis refers to the lysis of gram-negative bacteria by the complement protein complex known as the Membrane Attack Complex or MAC. The pores introduced into the outer membrane and possibly the cytoplasmic membrane of gram-negative bacteria my MAC results in their lysis. The LPS of the cell wall is the principle target for complement in gram-negative bacteria by activating the alternative complement pathway (def) and serving as a binding site for C3b as well as the site for formation of MAC (see Fig. 3). Some gram-negative bacteria, such as Salmonella (inf), lengthen the LPS O-polysaccharide side chain and this prevents the MAC lysis of the bacterium (see Fig. 4).
• Some gram-negative bacteria attach sialic acid from host cells to the LPS O antigen (see Fig. 2) and this prevents the formation of the complement enzyme C3 convertase that is needed for the eventual formation of all the beneficial complement proteins such as C3b, C5a, and MAC. Blood-invasive strains of Neisseria gonorrhoeae (inf), as well as Bordetella pertussis (inf) and Haemophilus influenzae (inf) are examples of Gram-negative bacteria that are able to alter their LPS in this maner.
• Neisseria meningitidis (inf) and Group B Streptococcus (inf), on the other hand, produces capsular polysaccharides composed of sialic acid and as mentioned above, sialic acid prevents MAC lysis.

For further information on bacterial pathogenesis, see the online Microbiology Web Textbook at the University of Wisconsin-Madison.

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