Pathogenic E. coli Infection Mechanism

Watch this three-part animation to see the molecular tricks that an infectious strain of Escherichia coli uses to infect your gut. E. coli are common, generally harmless bacteria, but certain less-common strains of E. coli can cause serious illness. An E. coli strain that's capable of infecting the intestinal tract is called enteropathogenic E. coli. Infection by enteropathogenic E. coli can cause severe diarrhea and can even result in death.

Part 1: A bacterium latches on to the surface of an intestinal cell

The surface of epithelial cells of the intestine is covered with microvilli, finger-shaped extensions of the cell that vastly increase the surface area for absorbing nutrients. In the animation, a single E. coli bacterium (purple) latches on to the surface of an intestinal epithelial cell (brown) using long, tetherlike pili. Pili are made of strands of long protein filaments that can adhere to the microvilli on the surface of intestinal cells.

Once in contact with the bacterium, the microvilli disappear from a patch of the cell surface, the bacterium comes into closer contact with the intestinal cell surface, and the next phase in the infection process begins.

Part 2: The bacterium injects receptor proteins into the intestinal cell

The tethered bacterium now uses a specialized injector system to deliver some of its own proteins into the cell that it is invading. The injector systems that bacteria use are fascinating and are composed of several different proteins. In this case a Type III injector system is used, which is specialized for pumping things into other cells. The bacterium uses the injector system, much like a syringe, to introduce several bacterial proteins into the intestinal cell that force it to cooperate in its own infection.

A needlelike tube (purple) called EspA projects from the bacterium to the intestinal cell surface. Now two proteins (green) named EspB and EspD travel through the tube to form an opening in the intestinal membrane through which additional bacterial proteins can move into the cell. With the tube and pore complete, the bacterium now injects a protein called Tir (red) into the cell. The Tir proteins insert themselves into the intestinal cell membrane. A portion of the Tir protein projects beyond the cell surface and binds to a protein on the bacterial cell surface called intimin (blue cups). Now the membranes of the intestinal cell and the bacterium are locked together, and the intestinal cell is in big trouble. The Tir proteins become phosphorylated by intestinal cell proteins (blue balls). The stage is set for the next step, pedestal formation.

Part 3: Intestinal cell forms pedestal for bacterium, and infection follows

The bacterium is now firmly bound to the intestinal cell surface via the interaction between the Tir and intimin proteins. Pedestal formation, a very active and striking process, begins. Another intestinal cytoskeletal protein (orange booties) binds to a portion of the bacterial Tir protein that is inside the cell. Once these proteins bind, long strands of actin (yellow balls) start to form. The actin filaments build up directly beneath where the bacterium is bound to the intestinal cell. As the actin filaments lengthen, they push the cell membrane upward, and the bacterium becomes perched atop a dramatic pedestal formed by the intestinal cell.

Once many enteropathogenic bacteria have adhered to the intestinal lining, symptoms of the infection (diarrhea) commence.

Pathogenic E. coli Infection Mechanism Background

Bacteria are small, single-celled organisms whose genetic material is not enclosed in a special nuclear membrane. For this reason, bacteria are called procaryotes (meaning prenucleus). Most bacteria can live inside the human body without causing any symptoms of disease. Bacteria that do cause disease are called "pathogenic." The invasion of the body by pathogenic bacteria is referred to as infection.

This animation looks at the first steps of infection of the human intestinal tract by enteropathogenic Escherichia coli. This bacterium is the major cause of diarrhea in small children in developing countries.

Once a pathogenic bacterium has gained entry to a host, it has to have some means of attaching itself to host tissues. Most pathogenic bacteria have surface molecules called adhesins or ligands that bind to preexisting cellular receptors. However, enteropathogenic E. coli manufacture receptors and inject them into the host cells. The bacteria then bind to these receptors. This novel mechanism of infection was discovered by HHMI international research scholar B. Brett Finlay, Ph.D. and his group in 1997.

E. coli Animation Teaching Tips

The animations in this section have a wide variety of classroom applications. Use the tips below to get started but look for more specific teaching tips in the near future. Please tell us how you are using the animations in your classroom by sending e-mail to edproducts@hhmi.org.

1. Use the animations to make abstract scientific ideas visible and concrete.

2. Explain important scientific principles through the animations. For example, the biological clocks animations can be used to demonstrate the fundamentals of transcription and translation.

3. Make sure that students learn the material by repeating sections of the animations as often as you think necessary to reinforce underlying scientific principles. You can start, restart, and play back sections of the animations.

4. Urge students to use the animations in accordance with their own learning styles. Students who are more visually oriented can watch the animations first and read the text later, while others might prefer to read the explanations first and then view the graphics.

5. Incorporate the animations into Web-based learning modules that you create to supplement your classroom curricula.

6. Encourage students to incorporate the animations into their own Web-based projects.

Pathogenic E. coli Infection Mechanism Credits

Director: Dennis Liu, Ph.D.

Scientific Direction: B. Brett Finlay, Ph.D.

Scientific Content: Satoshi Amagai, Ph.D.

Animators: Eric Keller, Satoshi Amagai, Ph.D.