Through perseverance, researchers at Ohio State have now found that certain disease-fighting drugs could be designed to prevent pathogens from entering the cell instead of having to kill the bug itself.

Abhey Satoskar, microbiology professor at OSU, and his colleagues tested the experimental drug against leishmania parasites, which infects humans and animals. The parasites are transmitted through the bite of sand flies, and cause leishmaniasis, a parasitic disease most common in tropical regions of the world, Satoskar said.

Pathogens are microorganisms such as fungi, viruses, bacteria and prions, which are known to cause diseases in animals and plants.

The mice used in the experiment lacked an enzyme called PI3K gamma. This particular enzyme plays an important role in white blood cell migration.

“If you have a mouse who’s genetically lacking the enzymes, those mouse would be more susceptible (to disease),” Satoskar said.

Or so he thought.

The results Satoskar and his colleagues obtained proved to be the exact opposite of what they had originally anticipated. Instead of growing ill, the mice showed resistance to the parasites.

“We were expecting that if you don’t have this enzyme in the mouse, the mouse will develop more serious diseases,” Satoskar said. “They didn’t become worse, in fact they became better.”

Satoskar said the results didn’t make any sense at the time, and he had to find out why the mice showed resistance.

Steve Oghumu, a post-doctoral fellow at OSU, worked with Satoskar on the project, said he was also surprised by the results of the experiment.

“It is a surprising result, a lot of times when we do experiments like this, you always expect the unexpected,” Oghumu said. “One of the most important thing is also finding out why these things happen the way they do.”

It took the researchers some time before they realized the same enzyme that helped white blood cells migrate could also be used by parasites to invade the cell.

Oghumu said it was perseverance that motivated him to work harder to find an answer for the outcome of the experiment.

“When you carry out experiments in the lab, you may not always expect (to see) what you see,” Oghumu said, “but also you have to keep persevering, you might not find an answer right there and then, but if you keep reading, keep doing more experiments … then you’ll be getting the solution to it.”

Typically, infectious-disease fighting drugs would target the pathogen and kill it, but Satoskar and his colleagues eventually found a new approach.

“The idea here is not to target the bug but to target the pathway in the host, which is used by the bug to survive and replicate and enter inside the cell,” Satoskar said. “Because if the bug cannot enter inside the cell, it cannot survive and cause disease.”

Satoskar said although the results of the experiment showed some promise, that does not mean a new disease-fighting drug has been created.

“We have just tested one molecule, which is important,” Satoskar said, “but that doesn’t mean that’s the drug for the disease … (it’s) just the start.”

Khalid Ebrahim, a first-year medical student, said he was impressed with the experimental findings.

“If you prevent (the pathogen) from entering, it’s actually very effective, you don’t have to worry about the bug changing or having any resistance,” Ebrahim said.