Research confirms novel strategy in fight against infectious diseases

January 9, 2012 by Emily Caldwell

New research shows that infectious disease-fighting drugs could be designed to block a pathogen's entry into cells rather than to kill the bug itself.

Historically, medications for infectious diseases have been designed to kill the offending pathogen. This new strategy is important, researchers say, because many parasites and bacteria can eventually mutate their way around drugs that target them, resulting in .

In this study, scientists showed that using an experimental agent to block one type of an enzyme in cell cultures and mice prevented a specific parasite from entering white blood cells, a step required for the parasite to cause . This method applies to that must enter a to survive and do their damage. Some bugs can thrive in a host body outside cell walls.

The researchers tested the against Leishmania parasites, which are transmitted by the bite of infected sand flies. The pathogen causes a parasitic common in tropical and subtropical regions of the world, with an estimated 1.5 million new cases diagnosed each year worldwide.

"This represents a new way of thinking about treatment for . This was a to see whether this emerging strategy is viable," said Abhay Satoskar, professor of pathology at Ohio State University and senior author of the study. "We aren't claiming we have a new drug for treatment. If we know this strategy works, then drugs can be developed that target different pathways in the host that could be important for pathogen invasion and survival."

The research appears online this week in the early edition of the .

Leishmania essentially hijacks a host's white blood cells to cause a skin infection called cutaneous leishmaniasis, characterized by sores of various sizes that may or may not be painful.

The standard compounds used to treat the must be injected and can cause damage to veins and a host of unpleasant symptoms. The side effects, combined with the need to receive daily shots for three weeks, lead to poor patient compliance – which can then allow the parasites to develop resistance to the drugs.

To work around pathogens' abilities to circumvent treatment, scientists have begun developing agents that target specific elements of the infection process inside the host body. One such experimental drug is called AS-605240, and it targets one type of an enzyme that is activated when recognize an intruder and the host body initiates an immune response.

This enzyme, PI3K gamma, controls cell movement as well as changes to a cell membrane that enable a pathogen to penetrate the . AS-605240 blocks the activity of the gamma form of the enzyme, which in turn is expected to reduce the number of cells recruited to an infection site and allow few pathogens to enter into the cells that are recruited.

Satoskar and colleagues ran a series of experiments on animal to demonstrate that the PI3K gamma enzyme does indeed control white blood cell activity in the immune response to Leishmania mexicana infection and that the presence of the experimental agent significantly reduced the ability of the parasites to penetrate white blood cell walls. The agent also reduced the number of phagocytes – one type of white blood cell – that were recruited to the infection site, meaning the parasites had fewer chances to find cells that could host them.

Additionally, the researchers tested these same responses in mice, with the same results. They then compared AS-605240 treatment of Leishmania infection in mice with the current standard drug treatment, sodium stibogluconate. After two weeks of treatment of lesions on the mice, the effects of both the experimental agent and the standard treatment were very similar, and both treatments reduced the number of parasites within skin lesions when compared with untreated lesions. When the treatments were combined, the healing effects were stronger than they were in mice that received just one type of treatment.

From here, Satoskar wants to fine-tune the strategy and consider other host-based pathways that could be safely manipulated to prevent pathogens from causing infection. The findings in this work suggest that such a strategy could be used not just for treatment, but for prevention as well.

"There is no prevention for these kinds of diseases," Satoskar said. "If we had a drug that would reduce the amount of phagocytes coming to the site of infection after parasites enter the skin, that would lead to a less severe infection that the body could probably control on its own."

Some people can self-heal from a Leishmania infection, but the time it takes is unpredictable so infections are typically treated, he said.

Explore further: What parasites eat is the key to better drug design

Related Stories

What parasites eat is the key to better drug design

August 4, 2011
A new study has revealed in unprecedented detail how parasites use different nutrients needed for growth, providing University of Melbourne researchers with unique drug targets against Leishmania, a tropical parasite that ...

Researchers identify new cell that attacks dengue virus

May 16, 2011
Mast cells, which can help the body respond to bacteria and pathogens, also apparently sound the alarm around viruses delivered by a mosquito bite, according to researchers at Duke-NUS Graduate Medical School in Singapore.

Recommended for you

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.