I. BACTERIAL PATHOGENESIS

B. VIRULENCE FACTORS THAT PROMOTE BACTERIAL COLONIZATION OF THE HOST

3. The ability to invade host cells

Fundamental Statements for this Learning Object:

1. Some bacteria produce molecules called invasins that activate the host cell's cytoskeletal machinery enabling bacterial entry into the cell by phagocytosis.
2. Entering a non-defense host cell can provide the bacterium with a ready supply of nutrients, as well as protect the bacterium from complement, antibodies, and other body defense molecules.
3. Some bacteria invade phagocytic cells, neutralize their killing ability, and turn them into a safe haven for bacterial replication.
4. Some bacteria kill phagocytic dendritic cells once they are engulfed and prevent those dendritic cells from activating the T-lymphocytes required for adaptive immunity.
5. These bacteria have the ability to co-opt the functions of the host cell for the bacterium’s own benefit. This is done by way of bacterial secretions systems that enable the bacterium to directly inject bacterial effector molecules into the cytoplasm of the host cell in order to alter its cellular machinery or cellular communication.

 

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.

We will now look at virulence factors (def) that enable bacteria to invade host cells.


Virulence Factors that Promote Bacterial Colonization of the Host

3. The Ability to Invade Host Cells

Some bacteria produce molecules called invasins (def) that activate the host cell's cytoskeletal machinery enabling bacterial entry into the cell by phagocytosis. Advantages of entering a human cell include:

a. providing the bacterium with a ready supply of nutrients.

b. protecting the bacteria from complement, antibodies, and other body defense molecules.

 

In addition, some pathogenic bacteria:

a. invade phagocytic cells, neutralize their killing ability, and turn them into a safe haven for bacterial replication (see Fig. 1).

b. kill phagocytic dendritic cells (def) once they are engulfed and prevent those dendritic cells from activating the T4-lymphocytes (def) and T8-lymphocytes (def) required for adaptive immunity.

Invasins of Salmonella (inf), Shigella (inf), and enteroinvasive strains of Escherichia coli (EIEC) (inf) , for example, allow these bacteria to enter epithelial cells of the colon. These bacteria, like many involved in infection, have the ability to co-opt the functions of the host cell for the bacterium’s own benefit. This is done by way of bacterial secretions systems that enable the bacterium to directly inject bacterial effector molecules into the cytoplasm of the host cell in order to alter its cellular machinery or cellular communication.

The most common type is the type 3 secretion system (see Fig. 2). A secretion apparatus in the cytoplasmic membrane and cell wall of the bacterium polymerizes a hollow needle that is lowered to the cytoplasmic membrane of the host cell and a translocon protein is then delivered to anchor the needle to the host cell. Effector proteins in the bacterium can now be injected into the cytoplasm of the host cell. The delivery system is sometimes called an injectosome.

When these bacteria contact the epithelial cells of the colon, the type III secretion system delivers proteins into the epithelial cells enabling them to polymerize and depolymerize actin filaments (def). This cytoskeletal rearrangement is a key part of the pseudopod formation in phagocytic cells and is what enables phagocytes to engulf bacteria and place them in a vacuole. Thus the bacterium with its invasins is able to trick the epithelial cell into behaving like a phagocyte and engulfing the bacterium. The bacteria then replicate within the host cell.

We will now look at several examples of bacteria that use invasions to invade host cells.

1. It is thought that Shigella first transit the mucous membrane of the colon by passing through M cells. (M cells are phagocytic cells in the mucous membrane whose function is to sample microbes from the intestinal lumen and pass them on to the lymphoid tissue of the Peyer's patch in order to activate the immune defenses against intestinal microbes). Once across the mucosa, the Shigella use a type 3 secretion system to inject invasins into the underside of the epithelial cells to induce phagocytic uptake of the bacterium (see Fig. 3).

GIF animation of Shigella invading an intestinal mucosal epithelial cell.

 


Highlighted Bacterium:
Shigella

Click on this link, read the description of Shigella and be able to match the bacterium with its description on an exam.

For a movie showing Salmonella invading a human cell, courtesy of the Theriot Lab Website at Stanford University Medical School. "Salmonella typhimurium invading a fibroblast cell."

 


Highlighted Bacterium:
Salmonella

Click on this link, read the description of Salmonella, and be able to match the bacterium with its description on an exam.


Highlighted Bacterium:
Borrelia bergdorferi

Click on this link, read the description of Borrelia bergdorferi , and be able to match the bacterium with its description on an exam.

 

 

 

 

E-Medicine article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.

 

 

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 at http://faculty.ccbcmd.edu/~gkaiser/index.html.

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Last updated: October, 2018
Please send comments and inquiries to Dr. Gary Kaiser