Exciting new research reveals third alternative to fighting infectious diseases – Australian science

When it comes to fighting infectious diseases, there are two common solutions. These include using medications such as antibiotics to fight pathogens and parasites or reducing the risk of spread through preventive measures.

However, a recent collaboration between the University of Colorado Cancer Center and the University of Virginia led to a discovery demonstrating the effectiveness of a third alternative. This exciting new research aims to manipulate characteristics of the human body to eliminate the mechanism that allows pathogens to cause disease.

The findings not only demonstrate how cancer science’s approach can be applied to the field of infectious diseases, but will also have profound implications for a disease that causes many thousands of deaths worldwide.

What is Entamoeba Histolytica?

Parasites are organisms that live inside or on the surface of another organism, known as a host, in order to survive. They benefit by obtaining nutrients from or at the expense of the host. Some parasites do not infect the host, others reproduce, grow or produce toxins, which can lead to parasitic infestation and very unpleasant symptoms.

There are several ways to contract the parasite, but the most common methods of transmission are poor hygiene, contaminated food and water, unclean fruits or vegetables, and undercooked meat.

Entamoeba histolytica, or E. histolytica, is a single-celled parasite that kills human cells and causes a disease known as intestinal amoebiasis. Amoebiasis is a parasitic infection of the intestines that affects approximately 50 million people worldwide, causing more than 100,000 deaths per year.

According to the Centers for Disease Control and Prevention, only 10% to 20% of those infected with E. histolytica become ill with it. Symptoms are usually mild and include abdominal pain, loose stools and abdominal cramps.

A severe form of amebiasis, known as amoebic dysentery, is accompanied by fever, severe stomach cramps and frequent bloody and watery stools. This occurs when the parasite penetrates the intestinal lining and is a much more dangerous form of the disease. If the parasite enters your bloodstream, it can end up in the lungs, brain, heart, liver or other organs and cause abscesses and tissue destruction.

Transmission of E. histolytica

Entamoeba histolytica is transmitted by the fecal-oral route. Although amoebiasis can affect anyone, it is more common in those who live or have traveled to tropical countries with poor sanitation. Areas with high rates of amoebic infection include parts of Central and South America, Africa, Mexico and India.

Other groups at increased risk for amebiasis include people with weakened immune systems and other medical conditions, those who live in institutions with poor sanitation, and men who have sex with other men.

Current Solutions

There are currently two widely used strategies to protect people from infectious diseases. These include using medications such as antibiotics to fight pathogens and parasites or eliminating environmental factors that contribute to disease transmission.

In the case of E. histolytica, antibiotics can be used for treatment. Uncomplicated cases of amoebiasis are usually treated with a one-day course of antibiotics.

However, if the parasite is present in the intestinal tissues, then it is necessary to eliminate the damage to the infected organs. In these cases, surgery may be required. Amebiasis can be fatal if left untreated.

Preventive measures to prevent amoebiasis focus on proper sanitation. The CDC offers advice on steps to take when traveling to a country with poor sanitation conditions. This includes drinking bottled, boiled, or purified water, washing fruits and vegetables thoroughly before eating, and avoiding street foods, unpasteurized dairy products, ice cubes, or water fountains.

Exploring the third strategy

A new study demonstrates the effectiveness of a third strategy to combat infectious diseases. This involves manipulating host genes to eliminate the mechanism that allows pathogens to cause disease.

The collaboration on this study resulted from a conversation between Dan Theodorescu, MD, director of the University of Colorado Cancer Center, and William A. Petrie, Jr., MD, chief of the Division of Infectious Diseases and International Health at the University of Virginia.

The idea was to apply a revolutionary technique used in cancer research to the study of infectious diseases. Together with Chelsea Marie, Ph.D., a postdoctoral fellow in the Petrie Lab at Virginia, they sought to determine whether killing any one cell could provide immunity to Entamoeba histolytica by silencing genes found in human cells.

This was done using a technique called RNAi, which allowed them to create a library of bladder cancer cells with thousands of independent silent genes. These cultures were then infected with the parasite E. histolytica.

When this technique is used in cancer research, they look for genes that make cells more susceptible to chemotherapy when they are silent. For this study, the infectious agent was an analogue of chemotherapy.

Although the parasite managed to destroy many thousands of these independent cellular structures, a small number seemed to resist it. To find out whether these silent genes provided immunity to these cells or simply survived by chance, Marie retested those cells that survived.

This process was repeated over nine generations of cells, and during these generations of selection, the cultures became increasingly enriched in cells that lacked certain genes. Resistance genes were then identified using next generation sequencing.

This showed that many of these genes are involved in potassium transport, controlling the flow of potassium into and out of human cells. A follow-up experiment showed that new intestinal cells treated with E. histolytica exhibited potassium efflux just before cell death. This meant that those cells that were unable to transport potassium did not die.

The researchers then changed the direction of their experiments to confirm that this is what actually causes resistance to the parasite. They took new cells and blocked their ability to transport potassium with drugs. By blocking the outflow of potassium, they were able to produce cells that were resistant to the parasite.

Targeting the human genes that allow E. histolytica to cause disease is a major discovery. This demonstrates that cancer science approaches can be applied to the field of infectious diseases to study genetic mechanisms of resistance.