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

a. an overview of phagocytosis, the complement pathways, and antibacterial peptides

Fundamental Statements for this Learning Object:

1. For phagocytosis to occur, the surface of the microbe must be attached to the cytoplasmic membrane of the phagocyte through unenhanced or enhanced attachment.
2. Following attachment, the microbe must be engulfed and placed on a membrane-bound vesicle called a phagosome. The phagosome then becomes acidified to provide the correct pH for killing by lysosomal enzymes.
3. Lysosomes, containing digestive enzymes and microbicidal chemicals, fuse with the phagosome containing the ingested microbe and the microbe is destroyed. This is referred to as intracellular killing by phagocytes and happens when microbial numbers are relatively low.
4. If the the infection site contains very large numbers of microorganisms and high levels of inflammatory cytokines and chemokines are being produced, the phagocyte will empty the contents of its lysosomes by a process called degranulation in order to kill the microorganisms extracellularly. This is referred to as extracellular killing.
5. The body’s complement pathways consist of a variety of complement proteins that when activated participate in four important body defense functions: promoting inflammation, phagocyte chemotaxis, opsonization (enhanced attachment), and lysis of membrane-bound cells.
6. The body produces a number of antibacterial peptides that are directly toxic by forming pores in the cytoplasmic membrane of a variety of microorganisms causing leakage of cellular needs.

 

LEARNING OBJECTIVES FOR THIS SECTION

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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.

We will now look at virulence factors (def) that enable bacteria to resist innate immune defenses such as phagocytosis, the complement pathways, and antibacterial peptides. We will begin with an overview of these innate immune defenses.

5. The Ability to Resist Innate Immune Defenses such as Phagocytosis and Complement

a. An Overview of Phagocytosis, the Complement Pathways, and Antibacterial Peptides

1. An Overview of Phagocytosis

As will be seen in Unit 5, there are several steps involved in phagocytosis.

a. Attachment

First the surface of the microbe must be attached to the cytoplasmic membrane of the phagocyte. Attachment of microorganisms is necessary for ingestion and may be unenhanced or enhanced.

1. Unenhanced attachment is a general recognition of what are called pathogen-associated molecular patterns or PAMPs (def) - components of common molecules such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, and glucans common in microbial cell walls but not found on human cells - by means of glycoprotein known as endocytic pattern-recognition receptors (def) on the surface of the phagocytes (see Fig. 1).

html5 animation illustrating the function of endocytic pattern-recognition receptors on phagocytes. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

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For more information: Preview of pathogen-associated molecular patterns (PAMPs) from Unit 5

For more information: Preview of pattern-recognition receptors from Unit 5

2. Enhanced attachment is the attachment of microbes to phagocytes by way of molecules such as an antibody (def) molecule called IgG and two proteins produced during the complement pathways (def) called C3b and C4b (see Fig. 2). Molecules such as IgG, C3b, and C4b that promote enhanced attachment are called opsonins (def) and the process is called opsonization (def). Enhanced attachment is much more specific and efficient than unenhanced.

html5 animation illustrating the function of enhanced attachment by way of IgG. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

 

For more information: Preview of antibodies from Unit 6

For more information: Preview of the benefits of the complement pathways from Unit 5

b. Ingestion

Following attachment, polymerization and then depolymerization of actin filaments send pseudopods out to engulf the microbe (see Fig. 3) and place it in a vesicle called a phagosome (def) (see Fig. 4).

html5 animation showing ingestion and phagosome formation. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

 

You Tube Movie illustrating bacterial phagocytosis by a neutrophil.

 

During this process, an electron pump brings hydrogen ions (H⁺) into the phagosome. This lowers the pH within the phagosome so that when a lysosome fuses with the phagosome, the pH is correct for the acid hydrolases to effectively break down cellular proteins.

html5 animation showing acidification of the phagosome following ingestion. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

c. Destruction

1. Intracellular destruction

Finally, lysosomes (def), containing digestive enzymes and microbicidal chemicals, fuse with the phagosome containing the ingested microbe and the microbe is destroyed (see Fig. 5).

html5 animation showing intracellular destruction. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

 

2. Extracellular destruction

If the the infection site contains very large numbers of microorganisms and high levels of inflammatory cytokines and chemokines are being produced in response to PAMPs , the phagocyte will empty the contents of its lysosomes by a process called degranulation in order to kill the microorganisms or cell extracellularly.

html5 animation summarizing phagocytosis through unenhanced attachment. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

 

html5 animation summarizing phagocytosis through enhanced attachment. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

You Tube animation summarizing phagocytosis by a macrophage.

 

Concept map for Bacterial Colonization of Host Cell: An Overview of Phagocytosis and the Complement Pathways.

 

2. An Overview of the Body's Complement Pathways

Some bacteria are able to interfere with the body's complement pathways. The complement pathways (def) will be discussed in detail later in Unit 4, but a brief summary is relevant here.

There are three complement pathways: the classical complement pathway, the alternative complement pathway, and the lectin pathway. While the three pathways differ in the way they are activated, once activated they all produce the same beneficial complement proteins. Basically the complement proteins are a series of serum proteins that when activated participate in four important body defense functions. These include:

a. Inflammation

Inflammation is the means by which body defense cells and defense chemicals leave the blood and enter the tissue around an injured or infected site. Complement proteins known as C5a, C3a, and C4a lead to vasodilation, increased capillary permeability, and the expression of the adhesion molecules on leukocytes and the vascular endothelium. This enables leukocytes to adhere to the inner wall of the capillaries, pass between the endothelial cells, and enter the surrounding tissue. Vasodilation also enables a variety of defense chemicals in the plasma of the blood to enter the tissue. These defense chemicals include antibodies and complement proteins. C5a also causes neutrophils to release proteases and toxic oxygen radicals for extracellular killing of microbes.

html5 animation of a capillary prior to vasodilation. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

html5 animation showing vasodilation. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

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b. Phagocyte Chemotaxis

Complement proteins C3a and C5a are chemoattractants for leukocytes. Chemotaxis enables the phagocytes to move toward the infected area in order to remove microorganisms.

html5 animation summarizing early inflammation and diapedesis. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

html5 animation summarizing late inflammation and diapedesis. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

 

You Tube movie illustrating chemotaxis.

 

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c. Opsonization (Enhanced Attachment)

The complement proteins C3b and C4b are known as opsonins because they bind microbes to phagocytes (see Fig. 2). One portion of the molecule binds to microbial proteins while the other portion binds to receptors on phagocytes. In this way, microbes can be engulfed by phagocytes more effectively.

html5 animation showing the role of C5a in vasodilation, the chemotaxis of phagocytes towards C5a, and their attachment to the opsonin C3b as a result of the complement pathways. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

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d. MAC Lysis of Biological Membranes

A series of complement proteins known as the membrane attack complex or MAC put pores in cellular membranes resulting in lysis. This is used to kill such things as Gram-negative bacteria, virus-infected cells, and tumor cells.

For More Information: The Complement Pathways from Unit 5

html5 animation showing the formation of the Membrane Attack Complex (MAC) during the complement pathways. by Gary E. Kaiser, Ph.D. Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus This work is licensed under a Creative Commons Attribution 4.0 International License. Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html. Last updated: August, 2019 Please send comments and inquiries to Dr. Gary Kaiser

These processes will be discussed in greater detail in Unit 5.

Concept map for Bacterial Colonization of Host Cell: An Overview of Phagocytosis and the Complement Pathways.

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3. Antibacterial Peptides

The body produces a number of antibacterial peptides such as human defensins (def) and cathelicidins (def) that are directly toxic by forming pores in the cytoplasmic membrane of a variety of microorganisms causing leakage of cellular needs. They also activate cells for an inflammatory response. Defensins are produced by leukocytes, epithelial cells, and other cells. They are also found in blood plasma and mucus.

Some bacteria are able to resist phagocytosis and interfere with the body's complement pathways (def). In the next two sections we will look at the following virulence factors:

1. The ability to resist phagocytic engulfment (attachment and ingestion)

2. The ability to resist phagocytic destruction and serum lysis

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• QUIZ YOURSELF ON THIS SECTION

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Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.

Last updated: Feb., 2021
Please send comments and inquiries to Dr. Gary Kaiser