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.
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
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).
- A movie showing Shigella within a cell being propelled by actin-based motility, courtesy of the Theriot Lab Website at Stanford University Medical School. "Shigella flexneri associated with actin tails in PtK2 cells."
Once inside they escape from the vacuole into the cytoplasm and multiply. Once inside, Shigella produces a protease that cleaves tubulin, a major component of the microtubule cytoskeleton. The microtubules represent a barrier to bacterial movement within the infected cell and the protease breaks down this barrier.
Now they move through the host cell and spread to adjacent host cells by a unique process called actin-based motility whereby actin filaments (def) polymerize at one end of the bacterium producing comet-like tails that propel the Shigella through the cytoplasm of the host cell. When they reach the boundary of that cell, the actin filaments push the Shigella across that membrane and into the adjacent cell (see Fig. 3). Actin-based motility enables the bacteria to spread from cell-to-cell without having to encounter defense cells and antibodies. As the Shigella grow and spread within the epithelial cells, those epithelial cells die and provoke a strong inflammatory response leading to the symptoms of dysentery.
In addition, Shigella can induce the host cells to produce signaling molecules that attract phagocytic, antigen-presenting dendritic cells to the area. It enters the dendritic cells and uses them to carry the Shigella through the intestinal wall to the underside. It then uses its type 3 secretion system to inject effector proteins from the phagosome into the cytoplasm. These proteins trigger apoptosis or cell suicide of the dendritic cell. Killing the dendritic cells prevents them from presenting Shigella to T4-lymphocytes, a step required for the production of antibodies against the Shigella (see Fig. 4).